7 Radiochemistry By D. S. URCH Chemistry Department Queen Mary and Westfield College. Mile End Road London El 4NS 1 Introduction This section of Annual Reports will cover recent progress in radiochemistry but omit discussion of conventional properties of organic or inorganic substances which happen to be radioactive. General aspects of the subject are covered in Keller’s introductory text ‘Radiochemistry’,’ now available in English whilst current topics in radiochemistry have been reviewed2 in the second edition of ‘Isotopes Essential Chemistry and Applications’. A second edition of the classic ‘Chemistry of the Actinide Elements’ has also a~peared.~ An international conference4 on all aspects of radiochemistry was held in Mexico City in 1988 and a review has been published5 of the progress that has been made in the fifty years that have elapsed since the discovery of nuclear fission.2 Isotope Production 3H (Tritium).-Infra-red lasers have been used6 to enrich tritium containing molecules such as chloroform and dichloromethane whilst the tritium content of either liquid or solid hydrogen (deuterium) can be determined accurately7 by infra-red spectroscopy. Distillation (H20-3HH0)8and thermal diffusion (H2-3HH)9 have also been employed to enhance the tritium content of labelled molecules. “C.-When the [14N(p,a)’ ‘C] reaction is carried out in a nitrogen-hydrogen mixture (94.6%-5.6%) “C-methane is produced efficiently.” This proves to be a convenient first step in the production of carbon labelled radiopharmaceuticals.‘ C. Keller ‘Radiochemistry’ John Wiley and Sons New York USA 1981. ’J. R. Jones ‘Isotopes Essential Chemistry and Applications’ (RSC Special Publication No. 68) Royal Society of Chemistry London 1988. J. J. Katz G. T. Seaborg and L. R. Mom ‘Chemistry of the Actinide Elements’ Second Edition Methuen New York USA 1987. ‘7th Nuclear Chemistry Radiochemistry and Radiation Chemistry Symposium’ Institute Nacional de Investigaciones Nucleares Mexico City Zacatecas Univ. Mexico 1988. ’ L. Wiesner in ‘Jahrbuch der Atomwirtschaft’ 1989. ed. W. D. Muller and R. Hussner Verlagsgruppe Handelsblatt Dusseldorf Germany 1989 p. A55. K. Suzuki A. Yokoyama G. Fujisawa and N. Ishikawa Report (M-88-168) Japan Atomic Energy Research Institute Tokyo 1988.P. C. Souers E. M. Fearon R. K. Stump and R. T. Tsugawa Fusion Technol. 1988 14 850. A. Kaba R. Akai I. Yamamoto and A. Kanagawa J. Nucl. Sci. Technol (Tokyo) 1988 25 825. I. Yamamoto A. Matsuo and A. Kanagawa J. Nucl. Sci. Technol. (Tokyo) 1988 25 857. P. Landais and R. Finn Appl. Radial. hot. 1989 40 265. 117 118 D. S. Urch '*F.-The radioactive fluoride anion ["F]- is produced by the irradiation of "0 enriched water and considerable effort has been expended recently in optimizing target for its most efficient production. [18F]- can be removed from the aqueous solution in which it was made by electrochemical deposition on a carbon electrode,16 reversing the polarity liberates the labelled anion when required. Other reactions that have been used to produce "F are [19F(~,n)~'Fl'~ and the two-stage process that uses high energy tritons as intermediates [6Li(n,a)3H]-[ 160(3H,n)'8F].The latter process has the advantage that it can be initiated in a nuclear reactor,I8 no cyclotron or high energy accelerator is required. 22 Na.-This isotope can be produced by the deuteron bombardment of a magnesium target [24Mg(d,a)22Na] and then separated from the target material by ion exchange chromat~graphy.'~~~~ 28Mg.-Intermediate tritons are again involved in the production21 of this isotope by the neutron irradiation of lithium-magnesium alloys [26Mg(3H,p)28Mg] a photo- nuclear route has also been reported.22 Transition Metals-first ro~.-~~Fe with a very low "Fe contamination can be pro- duced by the a-particle bombardment of enriched chromium.23324 Isotopes of cobalt (57C0)and manganese (54Mn) are formed when a silver-iron target (56Fe enriched) is irradiated with deuterons.25 67 Ga.-This isotope can be produced26 by the proton irradiation of germanium targets that have been enriched with 70Ge and 72Ge and separated from the target material by heating to 1100°C in hydrofluoric acid vapour (a 'simple method' according to the authors!).72,73,75 Se.-The irradiation of arsenic (either as the element or oxide) with protons or deuterons initiates nuclear reactions which lead to the ejection of many neutrons and leave isotopes of ~elenium.~~,~' Optimum yields of 73Se were obtained with 3540MeV particles.29 'I 0. Solin J. Bergman M.Haaparanta and A. Reissel Appl. Radiat. Zsot. 1988 39 1065. l2 M. S. Berridge and R. Kjellstrom J. Labelled Compd. Radiopharm. 1989 26 188. l3 J. Bergman K. Aho M. Haaparanta A. Reissel and 0.Solin J. Labelled Compd. Radiopharm. 1989 26 143. l4 G. K. Mulholland R. D. Hichwa M. R. Kilbourn and J. Moskwa J. Labelled Compd. Radiopharm. 1989 26 192. T. J. Tewson M. S. Berridge L. Bolomey and K. L. Gould Nucl. Med. Biol. 1988 15 499. 16 D. Alexoff D. J. Schlyer and A. P. Wolf Appl. Radiat. Zsot. 1989 40 1. l7 G. A. Brinkman and A. Wyand Appl. Radiat. Zsot. 1988 39 1141. 18 S. Bulbulian F. de M. Ramirez J. L. Iturbe C. H. Collins and K. E. Collins Analyst 1989 114 349. 19 J. L. Q. de Britto M. A. V. Bastos R. F. da Silva and A. G. da Silva J.Radioanal. Nucl. Chem. Lett. 1988 127 31. 2o R. J. N. Brits and F. von S. Toerien Appl. Radiat. Isot. 1988 39 1045. 21 J. A. Velden Z. Kolar R. C. Vollinga and J. J. M. Goeiji J. Labelled Compd. Radiopharm. 1989,26,172 22 P. Polak A. Wijand and L.Lindner J. Labelled Compd. Radiopharm. 1989 26 173. 23 J. Zweit H. Sharma and S. Downey Appl. Radiat. Isot. 1988 39 1197. 24 P. Smith-Jones and R. Weinreich J. Labelled Compd. Radiopharm. 1989 26 159. '' P. M. Smith-Jones F. J. Haasbroek F. W. E. Strelow and R. G. Boehmer Appl. Radiat. Isot. 1988 39 1073. 26 A. F. Novgorodov A. Zelinski and A. Kolachkovski Radiokhimiya 1988 30,672. 27 A. Mushtaq S. M. Qaim and G. Stoecklin Appl. Radiat. Zsot. 1988 39 1085. 28 A. Mushtaq S. M. Qaim and G.Stoecklin J. Labelled Compd. Radiopharm. 1989 26 148. 29 R. Weinreich R. Schwarzbach Z. B. Alfassi and P. Smith-Jones J. Labelled Compd. Radiopharm. 1989 26 146. Radiochemistry 119 75Br.-When bombarded with helium-3 particles arsenic also looses neutrons thus [7'As( He,3n)7' Br] .30 *'Sr.-A similar type of process can be used to produ~e~'~~~ this positron emitting isotope of strontium from krypton [szKr(3He,3n)82Sr]. Transition Metals-second row.-A method for the production of 93m Nb by the decay of 93M0 and 93mM~ following the thermal neutron irradiation of 92M0 has been described.33 The heavier isotope of molybdenum 99M0,has been more extensively investigated as it is the precursor of 99mT~. A relatively simple way of producing it is from uranium fission products.34 Ion-exchange purification of labelled molybdate anions35 and the extraction of 99M0as a thiourea complex36 have both been reported recently.99mT~ can be obtained conveniently from the parent molybdenum isotope either by elution from a zirconium molybdate gel37 or by complex formation using methylethyl ketone.38 The radiochemical purity of 99mTc produced by such processes has been reviewed,39 with particular reference to the content of the long-lived isotope 99T~.40 When bombarded with very high energy a-particles molybdenum not only pro- duces isotopes of ruthenium with the loss of some neutrons4' but also a whole range of isotopes of other lighter elements 87Y,88,89Zr 90,92Nb 93M~, and 94,95,96Tc. 109 Cd is produced from '09Ag by deuteron bombardment of silver-iron targets.*' 125 Sb.-Neutron irradiation of tin leads to the formation of a P-emitting isotope which decays to '25Sb.Carrier free antimony42 can then be separated from the parent element using an anion exchange column. 10dine.-'~~I can be produced by the proton irradiation of either xenon43 or tel- lurium4 (123Te enriched [123Te(n,y)1231]). If tellurium-124 is bombarded with deuterons 1241is made.4' Techniques have been described46 for the extraction of the heavier isotope 13'1 from the fission products of uranium. 30 C. Loc'h and B. Maziere J. Labelled Compd. Radiopharm. 1989 26 169. 31 F. Tarkanyi S. M. Qaim and G. Stoecklin J. Labelled Compd. Radiopharm. 1989 26 153. 32 I. Huszar H.Youfeng J. Jegge and R. Weinrich J. Labelled Compd. Radiopharm. 1989 26 168. 33 A. D. Gedeonov and A. A. Nosov Zsotopenpraxis 1989 25 294. 34 R. 0. Marques P. R. Cristini D. P. Marziale E. S. Furnari and H. 0. Fernandez Bol. SOC.Argent. Radioprot. 1988 12 49. 35 (a) J. Buerck S. A. Ali and H. J. Ache Radiochim. Acta. 1989 46 151; (b) J. Buerck and A. H. A. Sameh 'Patent DE-3 616 391/A Germany (BRD) 1987. 36 S. A. C. Mestnik and C. P. G. da Silva Report PUB-248 Instituo de Pesquisas Energeticas e Nucleares Sao Paulo SP Brazil 1989. 37 Z. Aliludin M. Ohkubo and K. Kushita Report M-88-167 (Tokai Research Establishment) Japan Atomic Energy Research Inst. Tokyo 1988. 38 K. Svoboda Nukleon 1988 3 16. 39 E. Reich and K. W. Boegl Nuklearmedizin 1989 28 71.40 F. Budsky J. Prokop and F. Melichar Nukleon 1988 2 7. 41 M. K. Das B. R. Sarkar N. Ramamoorthy and R. S. M,ani Radiochim. Acta 1989 47 29. 42 Y. Maruyama and Y. Yamaashi Appl. Radiat. Zsot. 1988,39 1079. 43 (a) F. Tarkanyi Z. Kovacs S. M. Qaim and G. Stoecklin Radiochim. Acta 1989,47,25; (b)B. Scholten S. M. Qaim and G. Stoecklin J. Labelled Compd. Radiopharm. 1989,26,175;(c)R. Maag and A. Janett J. Labelled Compd. Radiopharm. 1989 26 171. 44 P. P. Dmitriev At. Ehnerg. 1988 64 118. 45 (a)R. M.Lambrecht M. Sajjad M. A. Qureshi and S. J. Al-Yanbawi J. Radioanal. Nucl. Chem. Lett. 1988 127 143; (6) H. L. Sharma J. Zweit A. M. Smith A. G. Smith and S. Downey J. Labelled Compd. Radiopharm. 1989 26 165. 46 N.D. Vaidya S. N. Shinde V. C. Nair and T. S. Murthy 'Radiochemistry and Radiation Chemistry Symposium' Department of Atomic Energy Bombay India 1988. 120 D. S. Urch Lanthanides.-When natural europium is bombarded with 100 MeV protons a range of gadolinium isotopes are formed47 (146,147&149 Gd) whilst the a-particle irradiation of holmium induces48 the [165H~(a,2n)'67Tm] reaction. Transition Metals-third row.-When samarium (144,147Sm), europium ("'Eu) or gadolinium (1s4,155Gd) targets are bombarded with neon (2",22Ne) nuclei49 in a cyclotron many new short lived isotopes of hafnium tantalum and tungsten are produced. The new atoms are removed from the production zone by a potassium chloride in nitrogen aerosol. 2.6GeV protons induce" a wide range of different spallation reactions in gold platinum and thorium targets producing radioactive isotopes of most of the elements in this row of the periodic table.Less exciting but arguably more useful is the development for radio-medical use of a Ix8Re generator based on potassium '88W-tungstate5' and also l9Irn Ir generatorss2 which utilize 19'Os (e.g. labelled potassium hexachloro-osmate absorbed on activated carbon52n). Heavy E1ements.-'O2Hg enriched mercury has been proposed44 as a target material for the production of 201T1 using proton bombardment. Such bombardment can also be used to produce bismuth isotopes from lead. After separation from the parent material these isotopes decay to give53 a good yield of '03Pb. The heavier '4n + 1' isotope of lead 211Pb can be isolated54 from the decay products of 219Rn,which in turn resulted from the decay of 223Ra (purified as the stearate).The heavier isotope of radium 228Ra can be extracted" from stocks of old thorium compounds by ion-exchange and electrolytic methods. A~tinides.-~~~h can be made56 by the alpha particle bombardment of highly enriched 235U,[235U( a,2n)237Pu]. The preparation of metallic berkelium (249Bk) albeit as a very thin film has been described57 and details of an ion-exchange procedure for the isolation of 250Bk from 254E~ have been given." Heavy ion bombardment of 238U(with l6O) and 242Pu (with "C) gives rise59 to isotopes of fermium (250Fm)and californium Cf). (2443245&246 47 N. A. Lebedev A. F.Novgorodov Ya. Slovak V. A. Khalkin and L. Ehkhn Radioisotopy. 1988,28,240. 48 F. Niu T. Ma and R. Teng J. Radioanal. Nucl. Chem. 1988 124 353. 49 (a) H. Bruchertseifer B. Eichler J. Estevez and I. Zvara Radiochim. Acta. 1989,47,41; (b)J. Estevez H. Bruchertseifer B. Eichler T. Kruz and I. Zvara Sou. Radiochern. 1988 29 751. so B. Szweryn W. Bruechle B. Schausten and M. Schaedel Radiochim. Acta. 1989 47 33. '' A. P. Callahan D. E. Rice and F. F. Knapp Jr. Nucl. Compact. 1989 20 3. 52 (a)C. Brihaye M. Guillaume and F. F. Knapp Jr. in 'Radioactive Isotopes in Clinical Medicine and Research' ed. R. Hoefer and H. Bergmann Schatteur Stuttgart Germany (BRD) 1988 p. 397; (b)C. Brihaye M. Guillaume S. Dewez F. F. Knapp Jr. D. E. Rice and A. P.Callahan J. Labelled Compd. Radiopharm. 1989 26 162. 53 T. N. Van der Walt and P. P. Coetzee Talanfa 1989 36 451. 54 R. W. Atcher A M. Friedman J. R. Huizenga and R. P. Spencer J. Radioanal. Nucl. Chem. Left. 1989 135 125. 55 L. D. Volynskii V. M. Garbuzov and V. A. Tsirlin Sou. Radiochem. 1988 29 629. 56 L. A. Pelevin A. D. Gedenov and B. N. Shuvalov Radiokhimiya 1988 30 806. 57 V. M. Radchenko A. G. Seleznev M. A. Ryabinin L. S. Lebedeva R. R. Droznik V. D. Shushakov V. A. Stupin and V. Ya. Vasil'ev Sou. Radiochem. 1988 29 549. 58 L. I. Guseva and V. V. Stepushkina Patent 1 293 889/A Moscow USSR 1985. 59 S. Usuda Report 1315 (JAERI Tokai Ibaraki) Atomic Energy Research Institute Tokyo Japan 1989. Rad iochemistry 121 3 Labelled Compounds Once produced it is necessary to incorporate radioisotopes into specific chemical compounds if they are to be of any use.By far and away the most important perceived use today is in nuclear medicine. The diagnostic potential of positron emitting isotopes and the medical desirability of short lived isotopes encourage nuclear physicists to seek out isotopes which combine these properties and stimulate chemists to invent rapid synthetic routes for their incorporation into ever more exotic compounds. Recent reviews conferences or symposia which have dealt with all aspects of or just some specific topics connected with the preparation of radiopharmaceuticals for use in nuclear medicine include ‘The 7th International Symposium on Radiopharmaceutical Chemistry’,60 a workshop ‘Synthesis and Application of Radioactively Labelled Organic Compounds’,61 a series of lectures under the general title ‘Isotopes Essential Chemistry and Applications’,2 a detailed review of radiopharmaceuticals labelled with short-lived isotopes62 and a discussion of future trends in radio pharmaceutical^.^^ This section of the Report will attempt to pick out recent developments in the production of labelled compounds which have some novelty or specific application and seek to eschew run-of-the-mill syn- theses of new labelled compounds by conventional routes and procedures.Tritium.-Tritium replacement of a halogen atom continues to be the most popular route to molecules labelled at a specific The general applicability of the method can be judged from the following by no means exhaustive list of compounds recently labelled in this way; ~trychnine,~~ hemimellitic betaxolol,66 ~iprofibrate,~~ acid,68 insulin,69 cadrala~ine,~’ ~hangrolin,~~ diter~alinium,~~ 2-deoxy-~-[2,6,6’-3H]gl~~ose,73 and nitrosoamino-pyridyl butanone derivative^.^^ The tech- nique is subject to many variations of both catalyst and conditions.Tritium gas is the normal reagent but the advantages of liquid or even solid tritium have been e~tolled’~ in the labelling of peptides and amino-acids radiation damage is low 60 ‘7th International Symposium on Radiopharmaceutical Chemistry’ Groningen Netherlands 1988. [published as J. Labelled Compd. Radiopharrn. 26 19891. 6’ Workshop ‘Synthesis and Application of Radioactively Labelled Organic Compounds’ Rossendorf Dresden Germany (DDR) 1988.62 G. Stoecklin in ‘Nuclear Medicine part IB Emission Computer Tomography with Short-lived Cyclotron Produced Radiopharmaceuticals’ ed. H. Hundeshagen J. Fitschen F. Helus K. Jordan D. Junker G. J. Meyer 0. Schober and G. Stocklin Springer Berlin Germany (BRD) 1988 p. 31. 63 M. Frier Med. Nucl. 1989 I 157. 64 D. E. Brundish and P. D. Kane J. Labelled Compd. Radiopharm. 1988 25 1361. 65 C. N. Filer and D. G. Ahern J. Labelled Compd. Radiopharm. 1989 27 309. 66 J. Allen and A. Tizot J. Labelled Compd. Radiopharm. 1988 25 931. 67 D. Johnston R. A. Ormiston and P. D. Slowey J. Labelled Compd. Radiopharm. 1988 25 1319. 68 M. Shimoni J. Azran and 0.Buchman J. Labelled Compd. Radiopharm. 1988 25 685. 69 A. Haensicke K. D. Kaufmann M. Beyermann J. Oehlke c‘. Kertscher M. Bienert H. Niedrich E. Mittag S. D. Bespalova and M. I. Titov Collect Czech. Chem. Commun. 1988 53 2936. 7n D. E. Brundish and P. D. Kane J. Labelled Cornpd. Radiopharm. 1988 25 1371. 7L P. Leon C. Garbay-Jaureguiberry S. Le Greneur R. Besselievre and B. P. Roques J. Labelled Compd. Radiopharm. 1988 25 1143. 72 X. Zhang Y. Bao and R. Ding Nucl. Tech. 1988 11 29. 73 J. Deschamps B. Rousseau and J. P. Beaucourt J. Labelled Compd. Radiopharm. 1988 25 1281. 74 J. Roemer J. Labelled Compd. Radiopharm. 1989 27 257. 75 J. C. Wiley Jr. D. H. T. Chien and N. A. Nungesser J. Labelled Compd. Radiopharm. 1988 25 707. 76 (a) C.T. Peng R. L. Hua P. C. Souers and P. R. Coronado Fusion Techno). 1988 14 833; (b) C. T. Peng R. L. Hua P. C. Souers and P. R. Coronado Report 97513 University of California Lawrence Livermore National Laboratory CA USA 1988. 122 D. S. Urch and neither peptide links nor aromatic rings are attacked. In the more conventional procedures palladium catalysts are often used (e.g. labelled pep tide^^^ or substituted purines78). Sometimes as in the preparation of labelled diester derivatives of bi~henyl,’~ a high-voltage discharge has proved effective. Tritiated water can be used as a source of tritium in catalysed exchange reactions as in the preparation” of [3H]-18-methylnogestrienon (10% Pd/C). Tritium gas can also be used directly to produce labelled compounds either by catalysed exchange (e.g.[3H]-desmethyl imipramine,81 arabino~y1-[6-~H]5-azacytosine~~) or by addition to a double bond. In the former case palladium oxide on barium sulphate proved an effective catalyst for the labelling of ~yronaridine~~ in solution. Tetramethyl- phra~ine~~ can be labelled in a similar way but using palladium on alumina and with the assistance of a microwave discharge. Such a discharge in tritium gas proved effective in the labelling of many steroids.85 Double bond reduction by tritium gas has the advantage that labelling takes place onl-y at specific sites. This procedure also benefits from catalytic assistance as in the production of labelled di-N- propylaminochromanes86 or ~-[3,4-~H,]ornithine.~~ Asymmetric tritiation leading to L-[~H]- N-a~etyltryptopophanamide,~~ has been accomplished using the rhodium- diPAMP complex as a catalyst.Other routes to labelled compounds can also involve reduction by the use of reagents such as tritiated sodium tetraborohydride. Compounds recently labelled in this way have included epoxide~,~~ prostaglandin^,^^ tetrahydroprot~berberines,~’ g-dea~inosine,~’and the juvenile hormone methyl [12 -3H]-( 10R)-10,11- epo~yfarnesoate.~~ Small reactive tritiated molecules are particularly valuable since they can be used to introduce a labelled group to a specific site in a larger molecule as part of a multi-stage synthesis. With this end in view new methods have been described for the preparation of high specific activity f~rmaldehyde~~ and also methyl iodide.95 2-bromo[ 1 -3H]ethano196 can be used to introduce labelled hydroxyethyl groups at sulphur or nitrogen sites.77 P. Pham A. Moustier. B. Rousseau and J. P. Beaucourt J. Labelled Compd. Radiopharm. 1988,25,901. 78 G. Cooper J. Bourrell M. Kaminek and J. E. Fox J. Labelled Compd. Radiopharm. 1988 25 957. 79 M. Yi S. Ding C. Zhang and J. Xie At. Energy Sci. Technol. 1987 21 212. 80 D. Wu S. He and Y. Ge J. Isof. 1988 1 50. 81 J. Exner K. Fuksova R. Krulik D. Pichova and J. Picha Radioisotopy 1988 29 178. 82 G. F. Taylor K. Zamani and J. A. Kepler J. Labelled Compd. Radiopharm. 1988 25 1073. 83 S. Jiang L. Zhang D. Zheng Z. Feng and Z. Wu Nucl. Tech. 1987 10 44. 84 S.Ding Z. Meng Z. Han and Y. Jin J. Nucl. Radiochem. 1988 10 42. 85 G. Z. Tang and C. T. Peng J. Labelled Compd. Radiopharm. 1988,25 585. 86 J. M. Cossery L. Pichat C. Perdicakis G. Coudert and G. Guillaumet J. Labelled Compd. Radiopharm. 1988 25 833. 87 V. Tolman Radioisotopy 1988 29 183. 88 H. Pinto-Alphandary C. Van Craeynest-Jimonet J. L. Morgat and P. Fromageot J. Labelled Compd. Radiopharm. 1988 25 1273. 89 F. Setiabudi F. Oesch and K. L. Platt J. Labelled Compd. Radiopharm. 1988 25 1209. 90 V. P. Shevchenko T. Y. Lazurkina and N. F. Myasoedov Radiokhimiya 1988 30,527. 9’ X. Zhang and L. Yang Nucl. Tech. 1988 11 24. 92 A. K. Singh and R. S. Klein J. Labelled Compd. Radiopharm. 1988 25 1219. 93 E. Wai-si and G. D. Prestwich J.Labelled Compd Radiopharm. 1988 25 627. 94 M. Coppo B. Rousseau and J. P. Beaucourt J. Labelled Compd. Radiopharm. 1988 25 921. 95 P. Parent Thesis ‘Synthesis of High Specific Activity Tritium Labelled Compounds’ Conservatoire National des Arts et Metiers (Dept. Biologie) Paris France 1986. 96 M. Verny and C. Nicolas J. Labelled Compd. Radiopharm. 1988 25 949. Radiochemistry 123 Two mechanistic studies have been reported on the tritium labelling process. The first97 concerns the ferric chloride catalysed exchange reaction between tritiated water and the aromatic hydrogens in benzene and toluene. During the initial stages of the reaction tritiation proceeded preferentially at the ortho-and para-positions in tolulene at rates about two hundred times faster than in benzene.The second was a theoretical investigation of the role of metallic catalysts in the Wilzbach gas exposure labelling method. Carbon.-Techniques for the preparation of molecules labelled with 1C99 and with 14C100 have been reviewed. The former because of its twenty minute half-life poses the greater challenge to the synthetic chemist. Hot-atom reactions within the cyclo- tron can lead to "C being produced"' as labelled carbon dioxide. This can either be used directly (e.g.by reaction with trimethylsilyl derivatives followed by lithium aluminium hydride reduction to give "C-methyl as in the syntheses of the labelled D receptor antagonist SCH 23390102 and [1'C]-chlorpromazine;'03or via a Grignard reaction to form acetate which can then be used to form ["Clacetyl coenzyme A)'04 or converted to that most versatile of intermediates "C-methyl iodide.This reagent has been used to label many large and complex molecules for diagnostic studies in nuclear medicine thymidine,lo5 N-["Clmethyl labelled sertraline,lo6 nomifen- sine,lo7 and pyrilaminelo8 as well as a dopamine D receptor antagoni~t'~' and the benzodiazepine receptor antagonist Ro 15-1788."O A method for the rapid prepar- ation of ''C-labelled nitroalkanes,' ' ' especially nitromethane,' l2 has been described. These compounds can be used in further reactions such as the synthesis of ~-[1- "C]glu~ose."~ Other molecules that have been labelled with "C have included [3-"C]propionic acid,'14 sodium thiocyanate,"' [isopropyl-"C]nimodipine,"5 91 K.Oohashi K. Mori and K. Hirano J. Radioanal. Nucl. Chem. Lett. 1989 135 419. 98 Z. Meng S. Ding B. Liu and Y. Jin J. Nucl. Radiochem. 1988 10 180. 99 C. Crouzel Report Conference 9631 Centre d'Etudes Nucleaires de Saclay 91 Gif-sur-Yvette France 1988. 100 L. Pichat Radioisotopy 1988 29 9. 101 T. J. Ruth K. Pedersen C. Morin G. Ryley and C. Morrison J. Labelled Compd. Radiopharm. 1989 26 460. 102 S. Ram R. E. Ehrenkaufer and L. D. Spicer Appl. Radiat. hot. 1989 40 425. 103 S. Ram and L. D. Spicer Appl. Radiat. Isot. 1989 40 413. 104 G. Mannens G. Slegers R. Lambrecht and P. Goethais J. Labelled Compd. Radiopharm. 1988,25 695. 105 E. Poupeye A. de Leenheer G. Slegers P. Goethais and R. E. Counsell Appl.Radiat. Zsot. 1989,40 57. 106 M.-C. Lasne V. W. Pike and D. R. Turton Appl. Radiat. Isot. 1989 40 147. 107 J. Ulin A. D. Gee B. Laangstroem P. Malmborg and J. Tedroff Appl. Radiat. Isot. 1989 40,171. I 08 K. Yanai R. F. Dannals A. A. Wilson H. T. Ravert U. Scheffel S. Tanada and H. N. Wagner Jr. Nucl. Med. Biol. 1989 15 605. 109 A. A. Wilson R. F. Dannals H. T. Ravert and H. N. Wagner Jr. Appl. Radiat. Isot. 1989 40 369. 110 C. Halldin S. Stone-Elander J.-0. Thorell A. Person and G. Sedvall Appl. Radiat. Zsot. 1988,39,993. 111 K.-0. Schoeps S. Stone-Elander and C. Halldin Appl. Radiat. Zsot. 1989 40 261. 112 K.-0. Schoeps C. Halldin S. Stone-Elander T. Greitz and B. Laangstroem J. Labelled Compd. Radiopharm. 1988 25 749. 113 K.-0.Schoeps C. Halldin J.-O. Thorell S. Stone-Elander G. Blomqvist and L. Widen J. Labelled Compd. Radiopharm. 1989 26 86. 114 K. Niisawa K. Ogawa T. Nozaki and T. Hara J. Labelled Compd. Radiopharm. 1989 26 64. 11s S. Stone-Elander P. Roland C. Halldin E. Schwenner H. Boeshagen L. Widen and A. G. Bayer J. Labelled Compd. Radiopharm. 1989 26 238. 124 D. S. Urch amino acids,"6 and acyl chloride~."~ Carbon-1 1 can be introduced into aromatic rings using aryl chromium tricarbonyl intermediates.' l8 The preparation of 14C-labelled compounds continues apace but utilizing the standard procedures of synthetic organic chemistry. Even so it is of interest to note the study"' made of the alkali malonate catalysed exchange between 14C02 and carboxyl groups work undertaken to assess the utility of this reaction for the production of "C-acids.Nitrogen.-Despite a half-life of only ten minutes it has proved possible to incorpor- ate 13N into a couple of compounds butylamine12' and an opioid peptide.121 Oxygen.-The two minute half-life of "0 mitigates against much conventional chemistry but catalytic methods have been developed122 to convert 150-oxygen to 15 0-carbon dioxide. It is also possible to design systems for the production of 15O-~ater'~~ and even ['s0]b~tano1.124 Fluorine.-**F labelled fluorine gas produced by nuclear reactions in neon can be used directly to produce labelled compounds or introduced into electrophilic or nucleophilic reagents. In the former case site specificity can be achieved by the positioning of labile groups such as trimethylsilyl where required (e.g.N-['sF]fluoropyridinium triflate12'). In the absence of such direction fluorine gas gives rise to a much more random distribution of 18F than a reagent such as acetyl hypofluorite as experiments with phenylalanine tyrosine and dopamine have shown.'26 Recently a novel sequence of reactions has been rep~rted"~ which rapidly convert some "F-fluorine into the acetyl hypofluorite and the remainder into a tetra-alkylammonium fluoride thus neatly producing reagents for both electrophilic and nucleophilic reactions. Whilst "F-acetyl hypofluorite is quite selective in its reactions with aromatic rings producing 2-18F-phenylalanine 3-'8F-tyrosine,1267'28 and 2-"F-d0pa'~~ from unfluorinated starting materials the site for electrophilic attack can be directed by metallation using either tin or mer~ury,'~'as in the recently reported synthesis of ~-64 18F]fluorodopa.'30 Acetyl hypofluorite has also proved useful in producing'31 labelled derivatives of antitumor agents.116 (a) T. Guddat W. Herdering A. Knoechel and 0. Zwernemann J. Labelled Compd. Radiopharm. 1989 26 79; (b) K. J. Fasth G. Antoni P. Malmborg and B. Laangstroem J. Labelled Compd. Radiopharm. 1989 26 88. 117 S. K. Luthra D. Le Bars V. W. Pike and F. Brady J. Labelled Compd. Radiopharm. 1989 26 66. 118 M. J. Adam J. A. Balatoni and L. D. Hall J. Labelled Compd. Radiopharm. 1989 26 72. J. Szammer E. Simon-Trompler and L. Oetvoes J. Radioanal.Nucl. Chem. Lett. 1989 135 125. 120 G. W. Kabalka J. F. Green W. Zhe and M. M. Goodman J. Labelled Compd. Radiopharm. 1989,26 90. 121 H. Saji D. Tsutsurni J. Konishi A. Yokoyama Y. Kiso and T. Mimoto J. Labelled Compd. Radiopharm. 1989 26 73. 122 (a) R. Iwata T Ido Y. Fujisawa and S. Yamazaki Appl. Radiat. Isor. 1988 39 1207; (b) R. Iwata S. Yamazaki Y. Fujisawa and T. Ido J. Labelled Compd. Radiopharm. 1989,26,157; (c) K. Strijckmans J. Sambre and F. Guchteneire J. Labelled Compd. Radiopharm. 1989 26 458. 123 Y. Miyake Y. Ichiya Y. Kuwabara M. Otsuka M. Wada and K. Masuda Kaku Igaku 1988,25,659. 124 G. W. Kabalka J. F. Green and G. McCollum J. Labelled Compd. Radiopharm. 1989 26 76. 125 F. Oberdorfer E. Hofmann and W.Maier-Borst J. Labelled Compd. Radiopharm. 1988 25 999. 126 H. H. Coenen K. Franken P. Kling and G. Stoecklin Appl. Radial. Isor. 1988 39 1243. 127 R. Chirakal G. Firnau and E. S. Garnett Appl. Radiat. Isot. 1988 39 1099. 128 M. Murakami K. Takahashi and Y. Kondo J. Labelled Compd. Radiopharm. 1988,25,773. 129 A. Luxen M. Perlmutter and J. R. Barrio J. Labelled Compd. Radiopharm. 1989 26 1. 130 M. J. Adam and S. Jivan Appl. Radiat. Isor. 1988 39 1203. 131 G. W. M. Visser A. T. Bijma J. A. R. Dijksman and J. D. M. Herscheid Appl. Radiat. Isor. 1989,40 47. Radiochemistry 125 Nucleophilic substitution using 18F- can be achieved by nitro group displacement (as in the preparation of ['8F]ritanserin132), by mesylate group displacement (a step in the production of ['sF]fluorothienylcyclohexylpiperidine'33),or by the newly developed method of replacement of a cyclic sulphamate (a technique used in the synthesis of labelled fluoro-analogues of N-methyl-~-aspartate'~~).A very con- venient way of handling the radioactive fluoride anion is for it to be adsorbed onto an aminopolyether resin'35 (Kryptofix 222). This has led to new synthetic routes for 2-deoxy-2-[ '8F]fluoro-~-galactose'36 and 3-[ "F]fluoro-1-( 2-nitro-l-imidazolyl)-2-propan01,'~~ being reported. Sulph~r.-~~S-methionine has proved a useful starting material for the preparation of labelled hornocy~teine'~~ and glycyrrhizic acid'39 derivatives whilst [35S]thiourea was used to introduce sulphur-35 into 2-mercaptobenzimidazoles.'40The preparation has also been reported of 35S-thiophosphate'41 and its incorporation into inositol triphosphate.Transition Metals-first row.-The preparation of 57C0labelled thyroxine'^^ and of [67Cu]cupric-bis(thiosemicarbazones)'43 for radioimmunoassay and for use as radiopharmaceuticals has been reported. Gallium.-The preparation of a series of 68Ga labelled radiopharmaceuticals has been reviewed,I4 with special reference to bifunctional molecules in which one section chelates with the gallium whilst another part has a specific biochemical role. Bromine.-82Br can be introduced into many organic molecules by the addition of [82Br]bromine to a double bond'45 or by aluminium trichloride catalysed exchange with labelled dioxane dibr~mide.'~~ In bromamine-T it was that bromide exchange was maximized at pH 2.A report has appeared recently'48 which describes methods for the preparation of molecules (e.g.bromospiperone and bromolisuride) labelled wth lighter short-lived positron emitting isotopes 75Br and 76Br. Yttrium.-Tumour associated monoclonal antibodies have been labelled with 90Y.149 132 C. Crouzel A. Denis M. Venet and G. Sanz J. Labelled Compd. Radiopharm. 1988 25 827. 133 D. 0. Kiesewetter K. C. Rice M. V. Mattson and R. D. Finn J. Labelled Compd. Radiopharrn. 1989 27 277. 134 (a) D. M. Wieland M. R. Kilbourn D. J. Yang E. Laborde D. L. Gildersleeve M. E. Van Dort J.-L. Pirat B. J. Ciliax and A. B. Young Appl. Radiat. Zsot. 1988 39 1219; (b) F. Brady S. K. Luthra and V.W. Pike Appl. Radiat. Isot. 1989 40 325. 135 P. M. Pojer Aust. NZ J. Med. 1988 18 490. I36 T. Haradahira M. Maeda Y. Kai and M. Kojima J. Labelled Compd. Radiopharm. 1988 25 721. 137 D.-R. Hwang C. S. Dence T. A. Bonasera and M. J. Welch Appl. Radiat. Isot. 1989 40 117. 138 K. Hamacher J. Labelled Compd. Radiopharm. 1989 27 344. 139 L. A. Baltina R. M. Kondratenko Yu. G. Kuvatov Yu. I. Murinov and G. A. Tolstikov SOC.Radiochem. 1988,30 271. 140 D. R. Doerge J. Labelled Compd. Radiopharm. 1988 25 985. 141 P. Folk E. Kmonickova L. Krpejsova and A. Strunecka J. Labelled Compd. Radiopharm. 1988,25,793. 142 S. Al-Awadi K. Adham M. Hassan and H. Abdul-Dayem J. Immunol. Methods 1988 108 27. 143 M. A. Green and E. John J. Labelled Compd.Radiopharm. 1989 26 351. 144 M. J. Welch Progress Report DOE/ER-60 512-3 Department of the Environment Washington DC USA 1989. 145 R. Otto Report TR2373 Centre d'Etudes Nucleaires de Saclay 91 Gif-sur-Yvette France 1988. 146 R. Otto Report TR2374 Centre d'Etudes Nucleaires de Saclay 91 Gif-sur-Yvette France 1988. 147 (a)V. R. S. Rao G. Erdtmann and H. Petri J. Radioanal. Nucl. Chem. Lett. 1989 135 247; (b) V. R. S. Rao G. Erdtmann and H. Petri J. Radioanal. Nucl. Chem. Lett. 1989 135 257. 148 C. Loc'h Thesis Conservatoire National des Arts et Metiers 75 Paris France 1988. 149 S. J. Mather D. M. Tolley and G. W. White Eur. J. Nucl. Med. 1989 15 307. 126 D. S. Urch Technetium.-The nuclear properties of 99mTc make it one of the most widely used isotopes in nuclear medicine.The relationship between its varied chemistry and possible radiopharmaceuticals has been extensively re~iewed.'~' Problems associated with the stability of technetium compounds have also been addressed.'" The use of specific types of technetium compounds in nuclear medicine has been discussed; nitrodo-c~mplexes,'~~ bi-and tri-dentate Schiff's bases,'53 and tetradentate bisaminobisthiol cornplexe~.'~~ In all cases the technetium originally present as the Tc"" pertechnate anion must be reduced before complex formation can take place. Stannous chloride is widely used -a cunning new te~hnique'~~ requires the pertech- nate solution to flow through a plastic tube the inner surface of which is covered with adsorbed stannous ions.Although the final oxidation state of the technetium is often not well established complexes of aminohippuric acids,156 salicyclic acid,15' cysteine,lS8 substituted iminodiacetic and gentamycin'60 have been prepared and used successfully. Other methods for the reduction of Tc valency have included sodium borohydride in the formation of phosphonate'61 and thiodiglycollic acid'62 complexes and electrochemical methods leading to complexes based on dithi01s.l~~ The preparation of many other complexes containing Tc- S bonds has been reported thioether~,'~~rnonothi0-/3-dicarbonyls,'~~2,3-dimercaptos~ccinates,'~~2,3-dithiophosphosuccinates etc.16' Attempts to determine the technetium valency in some of these complexes have been made by comparing the UV spectra of complexes made from 'reduced pertechnate' and from technetium chlorides of known stoichiometry.'68 Technetium can also be used to label much larger molecules such as To this end the development of bifunctional ligands which can both bind to the 150 (a) H.Spies and R.Muenze Med. Nucl. 1989 1,125; (b) K. Schwochau in 'Proceedings of the 2nd International Symposium on Technetium Chemistry and Nuclear Medicine' ed. M. Nicolini G. Bandoli and U. Mazzi Raven Press New York U.S.A. 1986 p. 103; (c) B. Johannsen Isotopenpraxis 1988 24 449. 151 L. R. Chervu B. D. Vallabhajosyula S. B. Chun and J. Mni J. Nucl. Med. Allied Sci. 1988 32 234. 152 J. Baldass J. Bonnyman and J. Kanellos see ref. 150 (b) p. 103. 153 (a) G.Bandoli and M. Nicolini ibid. p. 73; (b) A. Duatti A. Marchi L. Magon J. L. Vanderheyden and E. Deutsch ibid. p. 131. 154 A. D. Watson T. H. Tulip and D. C. Roe Ibid. p. 61. 155 D. J. Maddalena G. M. Snowdon A. Awaluddin and P. M. Pojer in 'Proc. 5th International Symposium on Radiopharmacology' ed. A. E. A. Mitta C. 0. Canellas and R. A. Caro Comision Nacional de Energia Atomica Buenos Aires Argentina 1987 p. 75. 156 (a) B. Zmbova D. Djokic V. Bogdanova I. Tadzer B. Ajdinovic and M. Rastovac Appl. Radiat. Isot. 1989 40 225; (b) K. K. Bhargava Z. Zhuangyu S. B. Chun L. R. Chervu and M. D. Blaufox J. Labelled Compd. Radiopharm. 1988 25 943. 157 T. Soldi M. T. Valentini Ganzerli and M. DiCasa see ref. 150(b) p. 135. I58 A. H. Al-Kouraishi J.Radioanal. Nucl. Chem. 1988 125 213. 159 M. G. Arguelles C. 0.Canellas A. E. A. Mitta A. S. Leon E. S. Verdera and E. Leon ref. 155 p. 188. 160 S. H. Al-Kouraishi J. Radioanal. Nucl. Chem. 1988 125 203. 161 W. R. Heineman E. Deutsch and B. Scott in 'Proceedings of the 2nd International Symposium on Technetium Chemistry and Nuclear Medicine' ed. M. Nicolini G. Bandoli and U. Mazzi Raven Press New York USA 1986 p. 97. 162 S. A. Balakrishnan P. M. Pandey S Gaitonde and R. S. Mani ref. 150(b) p. 97. 163 I. De Gregori and S. Lobos Appl. Radiat. Isot. 1989 40 385. 164 G. F. E. Morgan J. Pope J. R. Thornback and A. E. Theobald ref. 150(b) p. 65. 165 H. Spies U. Abram R. Munze E. Uhlemann E. Ludwig and D. Scheller ref. 15O(b) p. 137. 166 H.Spies and D. Scheller ref. 150(b) p. 141. 167 S. Kovacheva and R. Georgieva Rentgenol. Radiol. 1987 26 32. 168 R. Stella and M. T. G. Valentini Appl. Radiat. Isot. 1988 39 1125. 169 D. Blok R. 1. J. Feitsma M. N. J. M. Wasser and E. K. J. Pauwels Nucl. Med. Biol. 1989 16 11. Radiochemistry 127 protein and chelate to technetium is most imp~rtant.'~' The labelling of both leukocyte^'^^ and fibrin~gen'~~ has been reported recently. with 99mT~ Ruthenium and Rhodium.-When ['03Ru]ruthenium trichloride reacts with ferrocene haloperidol the corresponding labelled ruthenocene compound is formed.'73 This decays to ['03mRh]rhodocene haloperidol which is rapidly oxidized in air to [103m Rhlrhodocinium halperidol. Indium.-" 'In is widely used to label monclonal antib~dies.'~"'~ The slightly heavier isotope '13"In (~~,~99.5 m) forms a complex with 3,3,10,10-tetraethyl-1,2-dithio-5,8-diazacyclodecanehydrochloride175which can be used as a myocardial imaging agent.10dine.-'~~I made by the [124Te(p,2n)'231] reaction'76 is widely used for the labelling of iodo-compounds by exchange with the iodide anion as in the preparation of [1231]rn-iodobenzylguanidine'77 and 154p-['231]iodophenyl)pentadecenoic or even the much larger glucose channel blocking agent MK-801.'34a In some cases as in the labelling of 2,5-dimethoxy-4-iodophenylisopropylamine,179 chloramine-T must also be used as an oxidant; the procedure is found to work equally well with 1231 and 1251. This method was also used in the preparation of 5-['251]iodo- ochratoxin.180 Iodide exchange at aromatic ring sites can be catalysed by transition metal ions.The mechanism of this reaction has been investigated181 and the results compared with CND0/2 based predictions. Procedures for the preparation of labelled amines 6413'I]iodohexylamine'82 or (*)-(4-[ '3'I]iodophenyl)pentyl-by iodide attack at a hydroxyl site have been developed with the assistance of trimethylsilyl polyphosphate or thallium trifluoroacetate. A new synthesis has also been reported'84 of [13' Iliodomethane. Heavier Elements.-Methods have been described whereby monoclonal antibodies can be labelled with '53Sm 185 or 203Pb.'86 Also details for the preparation of a I70 S. Z. Lever K. E. Baidoo A. V. Kramer and H.D. Burns Tetrahedron Left. 1988 29 3219. 171 (a) H. Kelbaek J. Linde and S. L. Nielsen Eur. J. Nucl. Med. 1988 14,620; (b) G. Endert U. Franke and P. Kleinert Med. Nucl. 1989 1 11. 172 M. G. Noto G. Rabiller C. Garrie Faget C. Fisman and A. Manzini ref. 155. p. 202. 173 M. Wenzel and Y. Wu Appl. Radiat. Zsot. 1988 39 1237. 174 (a) R. Reilly S. Houle K. Sheldon and A. Marks Appl Radiat. Isof.,1989,40,279; (b)A. M. Zimmer J. M. Kazikiewicz S. M. Spies and S. T. Rosen Nucl. Med. Biol. 1989 15 717; (c) M. Hartikka P. Vihko L. Hakalahti P. Torniainen R. Vihko and M. Soedervall Eur. J. Nucl. Med. 1989 15 157. 17s B. Liu Y. Jin L. Zhu M. Meng Y. Shi and H. F. Kung J. Nucl. Radiochem. 1988 10 162. 176 M. Sajjad R. M.Lambrecht and S. A. Bakr Nucl. Med. Biol. 1989 15 721. 177 B. H. Mock and R. E. Weiner Appl. Radiat. hot. 1988 39 939. 178 (a) M. Sajjad R. M. Lambrecht and S. Bakr Appl Radiat. Isot. 1989 40 428; (b) R. F. Verbruggen Appl. Radiat. Isot. 1988 39 1097. 179 C. A. Mathis A. T. Shulgin A. J. Hoffman and D. E. Nichols J. Labelled Compd. Radiopharm. 1988 25 1255. 180 D. Schmiedova B. Cerny and K. Veres Radioisotopy 1988 29 102. 181 T. Li Z. Meng X. Chang and S. Zheng Chin. J. Nucl. Sci. Eng. 1987 7 305. 182 G. Gopalokrishnan Y. W. Lee S. Selvaraj D. N. Abrams A. A. Noujaim and S. F. P. Man J. Labelled Compd. Radiopharm. 1988 25 879. 183 Y. W. Lee G. Gopalakrishnan S. F. P. Man and A. A. Noujaim J. Labelled Compd. Radiopharm. 1988 25 609.184 C. J. Cayetano F. P. Ramirez and M. E. Cortes ref. 4 p. 80. 185 M. E. Izard G. R. Boniface P. Sorby and K. Z. Walker Aust. NZ 1. Med. 1988 18 510. 186 S. C. Srivastava R. C. Mease G. E. Meinken L. F. Mausner and Z. Steokewski Report 41 800 Brookhaven National Laboratory Upton NY USA 1988. 128 D. S. Urch series of phosphonate derivatives of 186Re have been given.187 Tetramethyl lead labelled with 'loPb can be preparedIg8 by the electrochemical reduction of methyl iodide using a radioactive lead coated cathode. Subsequently trimethyl [*"Pb]lead chloride was also synthesized. Proteins have been successfully labelled with astatineIg9 by the expedient of first allowing the astatine (*"At) to react with a suitable organic reagent e.g.diazo-p-aminobenzoic acid and subsequently conjugat- ing the labelled complexes with the protein. 4 Hot-Atom Chemistry This section will consider chemical reactions of atoms and ions that have been excited translationally or electronically by nuclear transformations. The whole field since the discovery of the first such reaction by Szilard and Chalmers has recently been reviewed'" and the specific application of reactions of this type for the production of labelled molecules has been a~sessed."~ 3H.-The hot atom reactions of tritium in graphite,'92 boron carbide,193 and copper tetraphenylp~rphyrin'~~ have been investigated. In the first two cases hydr~gen''~~ and the annealing temperature had a critical effect upon the chemical state of the tritium.With the porphyrin attempts were made by the addition of helium as moderator to demonstrate that the relative energies of the tritium atoms substituting at aromatic sites were higher than those reacting at pyrrole sites. A similar type of comparison in which the reactions of recoil tritium atoms with mixtures of benzene hexane cyclohexane and perdeuterocyclohexane were showed that substitution was three times more probable at an aromatic than at an aliphatic site. Tritium decay can also produce chemical effects. A theoretical investigation of such decay in the hydrofluoric acid methylamine complex has shown'96 that the 3He atom is ejected immediately and that the complex is disrupted. In solid palladium tritide bubbles of helium-3 under high pressure can form and a solid-liquid phase transition can be detected by NMR at 250 K.'97 "C.-The reactions of carbon-11 atoms (or ions) made by a variety of different nuclear reactions have been in gaseous and solid mixtures of water- ammonia water-methane and ammonia-methane with a view to simulating the primary reactions of carbon atoms from the Sun and cosmic 'rays' in comets and in the upper atmosphere.187 M. G. Noto R. A. Amor D. A. Caviglia M. T. Ratner A. M. Schroder J. C. Rocco and A. C. Mancini ref. 155 p. 184. 1nn J. S. Blais and W. D. Marshall Appl. Radiat. Isot. 1988 39 1259. 189 C. Yi J. Jin and S. Zhang J. Isot. 1988 1 15. 190 K. S. Venkateswarlu Proc. Indian Natl. Sci. Acad. Part A, 1988 54 798. 191 K. Berei L. Vasaros and I.Kiss Kern Koezl. 1988 68 22. 192 (a)T. V. Tsetskhladze L. I. Cherkezishvili and N. Ya. Tsibakhashvili Zh. Fiz. Khim. 1988 62 1690; (b) M. Saeki and N. M. Masaki Radiochim. Acra. 1989 46 163. V. A. Barnov K. Sh. Bobokhidze L. Sh. Nadirashvili and T. V. Tsetskhladze At. Ehnerg. 1988,64,441. G. Izawa K. Shirahashi Y. Murano and K. Yoshihara Radiochim. Acta. 1989 46 191. 193 194 19s K. Oohashi J. Radioanal. Nucl. Chem. Lett. 1988 128 181. 196 Z. Zhu H. Zhao and D. Wang Acta Sci. Nat. Uniu. Pekin. 1988 24 411. 197 G. C. Abell and A. Attalla Fusion Technol. 1988 14 643. 19* B. Nebeling Thesis Cologne University (Chemistry Dept. Nuclearchemistry) Cologne Germany (BRD) 1988; also Report -2245 Kernforschungsanlage Julich GmBH Germany (BRD) 1988.Radiochemistry 129 13 N.-When recoil nitrogen-13 atoms react with materials such as propionic acid labelled ammonia and nitrogen acids are formed.'99 The relative yields of these products are as might be expected from previous work with recoil nitrogen greatly influenced by radiation effects. The yields are also affected by the phase of the reactant as radical reactions can proceed more quickly in the liquid than in the solid. 32 P.-Recoil phosphorus reacts with mixtures of carbon tetrachloride-tetramethyl compounds X(CH3)4 with X = Si Ge Sn and Pb to give labelled methylphos- phonic and mono- di- and tri- chloromethylphosphonic acids;200 in carbon disul- phide-alkanol mixtures labelled 0,O-dialkyldithiophosphates are formed.201 36 C1.-The (n,y) reaction in chloro-compounds generates recoil 3xCl.In bromotri- chloromethane 46% of the radioactive chlorine is found202 in organic combination a figure unaffected by iodine scavenger. The same effect was observed in ortho-and para-chloromethylfluorobenzenes. Iodine was effective however in reducing organic yields in the ortho-and para-trifluoromethylchlorobenzenes.203Relative reactivities of different molecules were evaluated from mixtures using the Kontis- Urch model. Transition Metals.-Mishra and Singh204 have suggested a mechanism for the reac- tion of 56Mn with permanganate and related ions which has provoked2" criticism. In iron phthalocyanine recoil manganese gives up to 6% labelled complex if the reaction is carried out in the solid phase but 0% in solution.206 When potassium chromate is irradiated with neutrons recoil "Cr is produced.The chromium atoms come to rest in a variety of valence states which depend upon chemical environment temperature radiation damage etc. In a recent experiment to determine the 'original' distribution of valence states a mixture of magnesium oxide and potassium chromate was the idea being that Cr"' would be both absorbed and not oxidized on the magnesium oxide. A two fold increase in the amount of trivalent chromium was observed indicating that most recoil chromium is trivalent at first. A much more direct way of studying the initial valence state of an atom in a solid matrix is to use if possible Mossbauer spectroscopy. This has been done for s7Fe produced by electron capture from 57C0 in K[CoF3] and K[NiF3];208 evidence is found for the stabilization of Fe"'.In [57Co]cobalt( 11) iodate the Fe" :FeIrr ratio was found209 to be 0.47.The same method has been used2" to study the fate of 57Fe on ion-exchange materials and zirconium phosphide. Neutron irradiation of ferrocene gives a high yield of labelled parent compound.211 Upon dilution this falls to almost zero 199 Y. Sensui and K. Tomura J. Radioanal. Nucl. Chern. Lett. 1988 128 359. 200 A. N. Bogushevskij and N. I. Lebedev Radiokhirniya 1988 30 567. 201 A. M. Makarov G. K. Genkina and T. A. Mastryukova Sou. Radiochem. 1988 30 267. 202 N. Chandrasekhar and B. S. M. Rao ref. 162 p. 210. 203 N. Chandrasekhar and B.S. M. Rao Radiochirn. Acta 1989 46 25. 204 S. P. Mishra and J. Singh Indian J. Chern. Sect. A 1988 27 192. 205 H. Mueller J. Radioanal. Nucl. Chern. Lett. 1988 127 219. 206 P. Benzi M. Castiglioni and P. Volpe Radiochirn. Acta 1989 46 29. 207 J. M. Lo C. L. Tseng and S. J. Yeh J. Radioanal. Nucl. Chern. 1988 123 683. 208 M. Devillers J. Ladriere and D. Apers Radiochirn. Acra 1989 46 197. 209 Y. Watanabe K. Endo and H. Sano Bull. Chern. SOC.Jpn. 1988 61 2785. 210 I. E. Alekseev and S. I. Bondarevskii High Energy Chern. 1988 22 233. 21 1 R. Blackburn and T. Yassine Radiat. Phys. Chern. 1989 33 337. reaction. Recoil 59Fe behaves differently in phthalocyanine complexes where a 12% retention is observed206 in the solid and a remarkable 6% in solution.The chemistry of recoil 6oCoin metal complexes has been reviewed'" and a new kinetic theory analogous to that for solid state decomposition reactions advanced2I2 to rationalize annealing reactions involving this atom. A detailed study has been made213of the reactions of recoil 6oCo with the tris(acety1acetonato) cobalt( 111) complex when adsorbed onto alumina. Substrate pore size plays a critical role in determining the nature of the labelled compounds. The chemistry of recoil copper atoms produced by the (n y) reaction in N-benzoyl- N-phenylhydroxylaminate and related complexes has been studied.214 Bromine.-The isomeric decay of 82mBr leads to the formation of an excited 82Br species. Detailed investigations have been made215 using solutions of bromomethane 1-bromobutane and 5-bromouridine to determine the nature and origin of this excitation.The results did not support the idea of an Auger induced 'Coulombic explosion' but suggested direct ionization and charge neutralization. The importance of the concomitant y dose has also been indicated216 by a series of experiments using different excitation sources. When recoil 80m Br reacts with bromotri-chloromethane nearly half of the radioactive bromine is found202 in organic combi- nation. Ruthenium.-The various isotopes of ruthenium produced by neutron irradiation have different recoil properties. These give rise to different 'parent yields' when ruthenocene is irradiated with ne~trons.~~Ru in particular undergoes internal conver- sion which initiates Auger ionization.The high yields of labelled ruthenocene which are observed even upon dilution may be explained2l1 by y cancellation and recoil absorption by the lattice. Further experiments with mixed metallocenes indicated217 that ion-molecule reactions play an important role in determining the final fate of the recoil atom. Tellurium.-As is so often observed in hot atom chemistry the matrix plays a dominant role in determining the mix of valence states observed218 for tellurium produced by spontaneous fission of 252Cf. The same effect is found when studying the chemistry of '27Te produced by the isomeric transition reaction. In this case the distribution of Te'" and Te"' was found to be solvent de~endent.~'~ Osmium.-Neutron irradiation of osmocene produces only small yields of labelled osmocene2'1 and even these are reduced upon dilution.As with the related metal- locenes it is proposed217 that the recoil chemistry can be understood in terms of ion-molecule reactions. 212 V. Ramshesh Nut1 Acad. Sci. Lett. 1987 10 429. 213 Y. Sakai A. Kageyama H. Nishioji and T. Tominaga Radiochim. Acta 1989 46 73. 214 C. Nakanishi Thesis Institute de Pesquisas Energeticas e Nucleares Sao Paulo SP Brazil 1987. 215 A. Ebrahim R. J. Meyer and E. P. Rack Radiochim. Acta 1989 46 65. 216 V. G. Dedgaonkar and R. S. Lokhande ref. 162 p. 201. 217 T. Yassine and R. Blackburn Radiat. Phys. Chem. 1989 33 341. 218 Z. Qi P. Zhang F. Wang and J. Guo J. Radioanal. Nucl. Chem.1988 125 271. 219 S. I. Bondarevskij and S. A. Timofeev Radiokhimiya 1988 30,803. Radiochemistry 5 Radiochemistry and the Environment The growing use of radioisotopes and of techniques based on nuclear reactions has led to an increasing concern with the impact of radioactive substances on the environment. This concern is manifest in many ways but the underlying desire is the reduction in exposure to radiation. Techniques are therefore being actively sought to remove radioactive substances from the environment and to ensure that they can be contained safely until their radioactivity is ‘negligible’. An alternative philosophy is that of rapid and extensive dilution and dispersion. (But is the world ready for ‘ban K-40’ and ‘C-14 out’ surely logical successors to the ‘Nuclear Power -No thanks’ and ‘Ban the Bomb’ campaigns).As is so often the case what is suitable for one isotope bearing in mind its nuclear and chemical characteristics global distribution total amount and rate of production will not be suitable for another. Much of the work to be reviewed here concerns the development of methods for removing specific isotopes and their subsequent immobilization (well thats the aim anyway). Two patents have recently been taken out for the removal of heavy metal ions using either a bacterially generated complexing agent220 or an insoluble carboxylated cellulose221 which would both sequester and chelate the ions. The behaviour of actinide ions in mineral waters has been extensively investigated covering topics such as complex formation by americium ions including complexes with humic acid,222 the hydrolysis of americium ions223 and the effect of radiolysis on the solution chemistry of plutonium.224 The removal of actinide ions from solution has also been investigated particular attention being paid to the adsorption onto calcite and related onto alumina,226 and also bentonite,227 as well as the effect that pH would have when granite228 was the substrate.The extent to which actinide ions can be ‘fixed’ in solids such as cement has been investigated,229 related research has measured the mobility of neptunium ions230 in glasses and ceramics. Similar investigations have been made for many lighter radioactive isotopes now being loosed into the environment as a result of the increased use of fission nuclear reactors for power generation.Recent papers have investigated the adsorption of many elements from aqueous solution of europium cobalt and caesium by fresh water sediment^,^^' of antimony(v) onto oxide and hydroxide surfaces,232 of 220 E. T. Premuzic US Patent document 4 780 238/A/ Washington DC USA 1988. 22 1 G. S. Elfine US Patent document 4 764 281/A/ Washington DC USA 1988. 222 (a) V. Moulin P. Robouch P. Vitorge and B. Allard Radiochim. Acta. 1988,44/45 33; (b) J. I. Kim G. Buckau and R. Klenze Report 01 788 Inst. fur Radiochemie der Technische Universitat Munich Germany (BRD) 1989. 223 S. Stadler and J. I. Kim Radiochim. Acta 1988 44/45 39. 224 K. Bueppelmann J.I. Kim and C. Lierse Radiochim. Acta. 1988 44/45 65. 225 T. C. Maiti M. R. Smith and J. C. Lad Radioact. Waste Manage. Nucl. Fuel Cycle 1989 11 269. 226 L. Righetto B. Marcandalli and I. R. Bellobono Radiochirn. Acta 1988 44/45 73. 227 B. Christiansen and B. Torstenfelt Radiochim. Acta 1988 44/45 219. 228 B. Torstenfelt R. S. Rundberg and A. J. Mitchell Radiochim. Acta 1988 44/45 111. 229 H. P. Thomason Report RW-88.094 Department of the Environment London UK 1988. 230 I. A. Ivanov A. N. Gulin V. M. Shatkov and E. A. Shashukov Radiokhimiya 1988 30,817. 23 1 S. M. Khalifa A. A. Halal H. F. Aly and A. M. El-Atrash Isotopenpraxis 1989 25 335. 232 S. Ambe Radiochim. Acta 1989 46 145. 132 D. S. Urch strontium and caesium by zeolites:33 and of fission fragment ions by silver iodide lanthanum oxalate and calcium and barium ~ulphate.~~~ Some ions of this type (cobalt and europium)235 form complexes with the simple organic ligands found in ground water whilst caesium [134Cs]and cobalt [“Co] coprecipitate with nickel(I1) hexacyanocobaltate( 111) thus facilitating their removal from solution.236 The mobility of nickel strontium iodine and caesium ions in bentonite has been studied as a function of pH.227 Other elements such as techenti~m~~~ pose by virtue of their wide range of possible valences greater complications when their water borne migration through rock formations is considered.Yet another aspect of the presence of radioactive materials adsorbed onto or chemically incorporated into minerals which should be considered is their behaviour upon fusion.The volatility of caesium and strontium from basalt as a function of temperature has been studied recently.238 Tritium poses special problems. Attempts to localize it as water of hydration in cements239 have failed (surprise?) but adsorption on iron based alloys has met with greater success.24o The oxidation of tritiated hydrogen to [3H]water has been investigated both in soils (reducing agents lower the rate of conversion to 3HHO)241 and in the gas phase,242 where UV irradiation increases the rate. Similar special environmental problems are associated with radioactive iodine (usually I3’I). For the most part this isotope will be airborne; methods have been developed to limit its release into the atmosphere based on adsorption on active or zeolite.244 The transport of radioiodine is determined by the extent to which it is adsorbed onto colloid particles in the air245 and its partition between the gas phase and The final chemical form (iodide or iodate) in which it is found depends greatly upon chemical especially pH (iodate in the sea and in tap water -iodide in rain and milk).The chemical and physical processes peculiar to radon that affect its interaction with biological systems have been reviewed;248 a complimentary piece of research has considered249 the fate of the daughter element polonium. 233 H. Mimura K. Akiba and I. Yamagishi Nippon Kagaku Kaishi 1989(3) p. 621. 234 M. Csaijka J. Radioanal.Nucl. Chern. 1988 122 333. 23s B. Skytte Jensen and H. Jensen Radiochirn. Acta 1988 44/45 45. 236 F. M. Mekhail K. Benyamin and K. Shakir Radioacf. Wasre Manage. Nucl. Fuel Cycle 1989 11 279. 237 T. Kanno Nippon Genshiryoku Gakkai-Shi 1988,30 313. 238 C. W. Sill Nucl. Chern. Waste Manage. 1988 8 97. 239 K. Nishimaki and T. Tsutsui Hoken Butsuri 1989 24 3. 240 M. Matsuyama K. Ashida H. Miyake K. Watanabe and Y. Araki Toyarna Daigaku Torichurnu Kagaku Senta Kenkyu Hokoku 1989 8 41. 24 1 M. Ichimasa Y. Ichimasa Y. Azuma M. Komuro K. Fujita and Y.Akita J. Radiat. Res. 1988,29 144. 242 S. Usami Y. Asai K. Hasegawa M. Matsuyama K. Watanabe and T. Takeuchi Toyarna Daigaku Torichurnu Kagaku Senta Kenkyu Hokoku 1989 8 75. 243 (a)W. P. Freeman M.P. King and J. L. Kovach ‘Proceedings 19th DOE/NRC Nuclear Air Cleaning Conference’ USDOE Assnt. Sec. for Environment Safety and Health (Nuclear Regulatory Comm.) Washington DC USA 1987 p. 237; (6) V. R. Deitz ibid. p. 265; (c) D. J. Gladden and M. Post ibid. p. 288; (d) H. G. Dillmann and H. Pasler ibid. p. 278. 244 Y. C. Fan T. Y. Lee C. S. Tan and C. M. Hsai ibid. p. 136. 245 H. Noguchi M. Murata and H. Matsui Proc. 7th Congress of the International Radiation Protection Association Australian Radiation Protection Society and Pergamon Press Sydney Australia 1988 p. 702. 246 G. J. Evans R. E. Jervis and E. G. Csillag J. Radioanal. Nucl. Chern. 1988 124 145. 241 Y. Muramatsu and Y. Ohmomo J. Radioanal. Nucl. Chern. 1988 124 123. 248 A.W. Castleman Jr. Report ER/60 668-1. Department of the Environment Washington DC USA 1988. 249 C. R. Phillips ref. 245 p. 894. Radiochemistry 6 Miscellaneous Detection.-An elegant new method has been developed for measuring the radio- activity that might be present in a minute droplet.250 The technique has been specifically developed for 14C labelled species. An electric field acts upon the charge the drop aquires as a result of radioactive decay just enough to counteract the force of gravity. In this way activities as low as 3 Bq have been detected. Simplified procedures have been reported for the analysis of high resolution y spectra from germanium detectors.251 The general problems of random and systematic errors and what is meant by the ‘minimum detectable amount’ of radioactivity have been considered252 and an improved geometry for the detection of a radiation has been developed.253 The kinetic and thermodynamic problems associated with assemblies of only a very few atoms have been considered254 and modifications to the laws of mass action etc.proposed based not on concentrations but the probability of finding a particular species in a given state and in a given phase. The detection of impurities in radiopharmaceuticals is of great concern as well as the accurate determination of the radioactivity of any particular preparation. Recent examples of these problems are to be found in papers dealing with the measurement of free 13’1 in labelled i~dohippuran~~~ and in or i~doamphetamin~~~ the determination of the specific activities of 1251 labelled thyroxine^,^^' or pertech- nate.258 The level of impurity associated with pertechnate anions produced from generator is also quite rightly of continuing concern.The storage of labelled compounds always poses problems due to autoradiolysis which will compromise radiochemical purity. The effects due to storage of adenosine triphosphate for many months have been studied259 and it is claimed that activities up to 400 GBq (thats about one tritium atom per molecule) can be kept in a ‘reasonably satisfactory’ state for more than a year! Spectroscopy.-When y radiation is internally converted the energy is utilized in the ejection of an electron. Depending upon the valence state and local environment of the atom in which this process occurs so will the kinetic energy of the electron be effected as is well established from photoelectron spectroscopy.Internal conver- sion electron spectroscopy can therefore be used with elements such as techentium260 to determine directly the valence state of an emitting atom. Resonance Raman 250 T. L. Ward E. J. Davis R. W. Jenkins Jr. and D. D. McRae Rev. Sci. Instrum. 1989 60,414. 25 1 H. B. Spitz R. Buschbom G. A. Rieksts and H. E. Palmer ‘Proceedings of 30th Annual Conference on Bioassay and Environmental Chemistry’. Pub NLO Inc. Cincinnati Ohio USA 1985. 252 A. Brodsky ibid. 253 D. Mascanzoni J. Radioanal. Nucl. Chem. 1988 124 431. 254 R. Guillaumont J. P. Adloff and A. Peneloux Radiochim.Acta 1989 46 169. 255 D. K. Ranganatha P. D. Soman and R. S. Mani ref. 162 p. 380. 256 A. Hammermaier T. Reichert E. Reich and K. W. Boegl Nuc. Compact 1988 19 113. 257 D. Ji and Y. He J. Nucl. Radiochem. 1988 10 36. 258 J. Silar and F. Budsky Jad Energ. 1988 34 290. 259 R. Lakshmi D. Padmanabhan A. U. Garana and K. V. Viswanathan ref. 162 p. 148. 260 (a) M. Fiser V. Brabec 0. Dragoun A. Kovalik M. Rysavy and N. Dragounova AppZ. Radiat. Zsot. 1988 39,943; (b) M. Fiser 0. Dragoun V. Brabec A. Kovalik M. Rysavy U. Mazzi A. Moresco F. Refosco and F. Tisato ref. 150(b) p. 57; (c) 0. Dragoun M. Fiser V. Brabec A. Kovalik A. Kuklik and P. Mikusik Czech. Patent 243 954/B1/ Prague Czechoslovakia 1988. 134 D. S. Urch spectroscopy has also been used261 to study technetium complexes.Tritium labelled compounds can be studied using tritium NMR,262 and the location of the tritium atom established. Applications.-Radioactive 1-iodohexane has been used to label tar from cigarettes (they were doped).263 This enabled the tar in the ‘mainstream’ smoke to be measured on a puff-by-puff basis! Muon Chemistry.-The capture of negative muons by organic molecules has been investigated.264 It was found that whilst the probability of capture was roughly proportional to the atomic number of the atom there were small variations which could be rationalized by ab initio molecular orbital calculations for the individual molecules. 261 A. Davison R. M. Pearlstein P. A. Mabrouk A. G. Jones and M. M. Morelock ref.150(b) p. 25. 262 (a)P. G. Williams Fusion Technol. 1988 14 840; (b) L. Zhang and J. R. Jones J. Isot. 1988 1 28. 263 J. N. Pritchard J. J. McAughey and A. Black J. Aerosol Sci.,1988 19 715. 264 M. K. Kubo Y. Sakai T. Tominaga and K. Nagamine Radiochim. Acta 1989,47 77.