26 Radiochemistry By DAVID S. URCH Chemistry Department Queen Mary and Westfield College University of London Mile End Road London El 4NS UK 1 Introduction This section of Annual Reports will consider recent progress in various aspects of radiochemistry but excluding the chemistry of the heavy radioactive elements and radiation chemistry. A few new books covering various aspects of the field have been published ‘Principles of Radiochemistry’,’ ‘Radiochemistry and Nuclear Methods of Analysis’,2 the third edition of Keller’s ‘Fundamentals of Radio~hemistry’~ and ‘Handbook of Hot Atom Chemistry’.& The launch of the latter was marked by an international seminar the proceedings of which were also published.4b An interesting review of eighty years of nuclear chemistry research in Hungary appeared re~ently.~ The various sections of this review will consider methods whereby specific isotopes may be made and/or purified the chemical effects of nuclear reactions the preparation of labelled compounds the effect of radiochemistry on the environment and finally a miscellaneous section.2 Isotope Production Many of the isotopes used in nuclear medicine are the daughters of long-lived isotopes. For convenience these isotopes are incorporated into some type of column from which the daughter can be eluted as and when required. A comprehensive and critical review of such ‘isotope generators’ has recently been published.6 Light Elements.-There is increasing interest’ in the production of 18F by the neutron irradiation of oxygen-containing lithium compounds [6Li(n,or)3H followed by ‘Principles of Radiochemistry’ ed.D. D. Sood N. Ramamoorthy and A. V. R. Reddy Indian Association of Nuclear Chemists and Allied Scientists Bombay India 1993. ‘Radiochemistry and Nuclear Methods of Analysis’ ed. W. D. Ehmann and D. E. Vance John Wiley and Sons New York USA 1993. C. Keller ‘Grundlagen der Radiochemie’ 3rd Ed Sauerlander Frankfurt-am-Rhine Germany 1993. (a) ‘Handbook of Hot Atom Chemistry’ ed. J. P. Adloff P. P. Gaspar M. Imamura A. G. Maddock T. Matsuura H. Sano and K. Yoshihara Kodansha Tokyo Japan and VCH Weinheim Germany 1992; (b) ‘Proceedings of the international seminar on the chemistry of high energy atoms’ ed. T. Matsuura Inst. Atomic Energy Rikkyo Univ. Yokosuka Kanagawa Japan 1993.I. Feher and I. Kiss Magyar Kemiai Folyoirac 1994 100 135. F. F. Knapp and S. Mirzadeh Eur. J. Nuciear Med. 1994 20 1151. ’ (a)J. Jimenez-Becerril D. Estevez and S. Bulbulian J. Radioanal. Nuclear Chem. 1994 187 419; (b) H. Kvaternik ‘Reactor-produced (“F) fluoride in the synthesis of (‘*F)labelled compounds’ Thesis Tech. Univ. of Vienna Vienna Austria 1991. 499 500 David S. Urch 160(3H,n)' 'F]. Tritium can be recovered' from irradiated lithium carbonate by distillation. The more usual route to "F is by ["O(p,n)'*F] using "0 enriched water but deleterious effects due to traces of metal ions have been reported' and improved results have been found' O using solid '0-enriched carbon dioxide. When water with only a low enrichment of "0 is irradiated with protons not only is "F produced but also 13N from the [160(p,a)'3NJ reaction.A careful choice of conditions" enables both labelled ["FI-fluoride and ["N]-nitrate(rr~,v) anions to be prepared simultaneously. 13N can also be made by the proton irradiation of carbon [12C(p,y)13N],12 if ethan01'~ is used as the target material ['3N]-ammonia results. The short-lived 16N can be made14 by the irradiation of water by fast neutrons [160(n,p)16N]. The positron emitter 38Kcan be made" in a low energy cyclotron by the proton irradiation of argon [38Ar(p,n)38K] whereas 63Ni requires the prolonged neutron irradiation of a 62Ni enriched target16 at high flux. Other transition metal isotopes 64Cu and 67Cu can be prepared17 from zinc targets.Zinc can also be used for the production of 67Ga when 68Zn is irradiated" with protons (28 MeV). 72Asand 73Se are both positron emitters and roles for both have been proposed in nuclear medicine. The former can be obtained from the decay of 72Se using an automated generator" and the latter is produced when copper arsenide2' is bombarded with protons. The low mass isotopes of bromine (75,2176,22and 7723)are also positron emitters with uses in nuclear medicine and can be made from arsenic by alpha particle irradiation. A new method for controlling the preparation of the radiopharmaceutical diagnostic agent * '"Kr has been described.24 82Kr is initially proton irradiated [82Kr(p,2n)' 'Rb]; the rubidium is then adsorbed on a cation exchange resin where it decays (T~,~ 4.6hr) to ""Kr.A procedure for the preparation of 82Sr from rubidium has been described25 but a mixture of 82Sr and 85Sr,26a together with isotopes of niobium,26b zirconium ("Zr) H. F. Rea F.A. Palma and F. M. de Ramirez J. Radioanal. Nuclear Chem. 1993 173 249. D. J. Schlyer M. L. Firouzbakht and A. P. Wolf Appl. Radiat. Isotopes 1993 44 1459. la M.L. Firouzbakht D. J. Schlyer S.J. Gatley and A. P. Wolf Appl. Radiat. Isotopes 1993 44,1081. R.A. Ferrieri D. J. Schlyer C. Shea and A. P. Wolf J. Labelled Compd. Radiopharm. 1993 32 118. V. I. Tchuev E. P. Derevyanko I.V. Ekaeva,V. G. Isotov,T. A. Katunina M. N. Klebanov,L. S.Larionov and N. S. Marchenkov ibid. 1993 32 470. l3 R.A. Ferrieri K. MacDonald D. J. Schlyer and A.P. Wolf ibid. 1993 32 461. l4 T. Akimoto T. Hirata and M. Narita in 'Radiation detectors and their uses' ed. M. Miyajima S. Sasaki Y. Yoshimura T. Iguchi and M. Nakazawa Nat. Lab. for High Energy Physics Tsukuba Japan 1993 p. 215. l5 S. M. Qaim G. Stoecklin F. Tarkanyi and Z. Kovacs J. Labelled Compd. Radiopharm. 1993 32,478. I' D. F. Williams G. D. O'Kelley and J. B. Knauer Radiochim. Acta 1994 64 49. S. Mirzadeh D.E. Rice and F. F. Knapp Jr. J. Labelled Compd. Radiopharm. 1993 32 474. l8 T. E. Boothe E. Tavano J. Munoz S. T. Carroll and P. M. Smith in 'New Trends in Radiopharmaceutical Synthesis Quality Assurance and Regulatory Control' ed. A. M. Emran Plenum Press New York NY USA. 1991 p. 169. D. R. Phillips V. T. Hamilton D. A. Nix W. A. Taylor D.J. Jamriska R. C. Staroski and R. A. Lopez Ref. 18 p. 173. 'O D. de F. Santos and R. Weinreich J. Labelled Compd. Radiopharm. 1993 32 464. C1. Brihaye M. Guillaume J.C. Depresseux D. Comar and J. Trumper ibid. 1993 32 445. 22 J. Mertens A. Hermanne D. Terriere and F. Lambert ibid. 1993 32 477. 23 F. Lambert and G. Siegers Appl. Radiat. Isotopes' 1994 45 11. 24 S. L. Regdos A. C. Mignerey N. R. Simpson and H. R. Adams Ref. 18 p. 451. 25 V. V. Golik,G. A. Kavkhuta L. F. Rozdyalovskaya L. A. Klokotskaya B. G. Luchkin and S. E. Chigrinov Vesti Acad. Navuk BSSR Sery. Fizika-Tekh. 1993 2 118. 26 (a)R. C. Heaton D. J. Jamriska Sr. and W. A. Taylor 'Process for strontium-82 separation' US Patent Doc. 5 167,938/A 1992; (b)D. R. Phillips D. J. Jamriska Sr. and V.T. Hamilton 'Recovery of niobium from irradiated targets' US Patent Doc. 5 296 203/A (1994); (c) R. C. Heaton D. J. Jamriska Sr. and W. A. Taylor 'Process for separation of zirconium-88 rubidium-83 and yttrium-88' US Patent Doc. 5,330 731/A 1994. Rad iochemistry 50 1 rubidium (83Rb) and yttrium (88Y)26c results from the proton irradiation of molybdenum. Other yttrium isotopes can be made27 using a 90Sr generator ("Y) or can be isolated28 from irradiated uranium (91Y). 95Zr is also found in neutron irradiated uranium. It decays to 95Nb and methodsz9 for the isolation and purification of this niobium isotope (chromatography ion exchange) have been described. Technetium.-Techniques for the preparation3' of 94mT~ (a short-lived positron emitting isotope) and its purification3' have been reported.Other light isotopes of technetium (95T~ can be made3' by gamma irradiation (50MeV) of 99Tc. and 96T~) Very much more effort has been directed towards the production of 99mTc and therefore towards ways in which 99Mo can be made. A popular source is spent fuel from nuclear reactors which contains 99Mo as a fission product. The problem is to extract pure 99Mo uncontaminated with any isotope of any other element.33 The use of low-enriched uranium (as the ~ilicide)~~ apparently facilitates the subsequent extrac- tion of 99Mo. New methods have been reported for the removal of non-fissioned uranium35 and for the separation of 99Mo from 132Te (another fission product).36 Another route to 99Mo is by the neutron irradiation of molybdenum but this has the disadvantage that only a small amount of 99Mo is produced.To some extent this problem may be overcome37 by concentrating the pertechnate solutions that can be eluted from columns made from neutron irradiated MOO,. Column design has also exercised people's minds of late the particular concern being to prevent the elution of molybdenum with the technetium. Chemical inc~rporation~~ of 99Mo into the gel of the column as molybd~phosphate~~ have both been suggested. or m~lybdocerate~' The preparation of the long-lived isotope 99Tc from neutron irradiated molybdenum trioxide has been de~cribed.~~ Finally another way in which 99Mo may be made42 is by the gamma (25 MeV) irridation of "'Mo ["'M~(y,n)~~Mo],but purification from niobium [100Mo(y,p)99Nb] is necessary.Heavy Elements.-'06Ru can be extracted from uranium fission products29b using ion exchange columns based on ammonium phosphomolybdate and stannic antimonate. A new method for the separation of "In from alpha bombardment of silver targets has " (a)B. T. Hsieh G. Ting H.T. Hsieh and L. H. Shen Appl. Radiat. Isotopes 1993,44,1473;(6)A. Dash and P. K. Bhattacharyya ibid. 1994 45 415. '' G. B. Maslova V. M. Gelis V. V. Milyutin and N. I. Polyakova Radiokhimiya 1992 34 78-82. 29 (a)N. R. Das K. Singh and S. Lahiri 'Nuclear and Radiochemistry Symposium' ed. V. Venugopal B. S. Tomar and D.D. Sood Dept. of Atomic Energy Bombay India 1992 p. 444; (6) A. Dash K.R. Balasubramanian and T. S. Murthy Ind.J. Techn. 1993 31 593. 30 R. J. Nickles B. T. Christian A. D. Nunn and C. K. Stone J. Labelled Compd. Radiopharm. 1993,32,447. 31 F. Roesch A. F. Novgorodov and S. M. Qaim Rudiochim. Acta 1994 64 113. 32 T. Sekine K. Yoshihara J. Safar L. Lakosi and A. Veres J. Radioanal. Nuclear Chem. 1994 186 165. 33 (a)S. A. Ali and H. J. Ache in 'Proc. Tnt. Meeting on Reduced Enrichment for Research and Test Reactors'. Argonne Nat. Lab. Ill. USA 1993,417;(b)S. L. Marshall L. Redey D. R. Vissers G. F. Vandegrift and J. E. Matos ibid. 443. 34 J. D. Kwok G. F. Vandegrift and J. E. Matos ibid. 434. 35 A. S. Rodriguez A. L. Ch. Acosta B. E. M. Lopez and L. A. Fucugauchi J. Radioanal. Nuclear Chem. 1994 178 417. 3h S.A. C. Mestnik and C.P.G. da Silva ibid. 1993 172 87.37 S. Seifert G. Wagner and A. Eckardt Appl. Radiat. Isotopes 1994 45 577. 3R S. P. Iyer D.V. S. Narasimhan L.N. Singh and R.R. Patel Ref. 29(a) p. 325. 39 M.T. El-Kolaly J. Rudioanal. Nuclear Chem. 1993 170 293. 40 M.A. El Absy A.I. Audah and I. M. El Naggar ibid. 1993 173 185. 41 W. Sun T. Wu J. Bao and M. Li Nuclear Power Engineering 1992 13 83. 42 M.G. Davydov and S.A. Mareskin Radiochemistry (New York) 1994 35 569 (Russian original Rudiokhimiya 1993 35(5) 91). 502 David S. Urch been reported43 whilst the heavier isotope '14Tn results44 from the neutron irradi- ation of 'I3In. 1231(positron emitter) is particularly useful in nuclear medicine and improvements in techniques for its production continue to be reported.45 An improved method for the purification of 137Cshas also been ann~unced.~~ 134La has potential as a radiopharmaceutical isotope and can now be easily obtained47 from a 34Ce gener- ator.Similarly 17'Lu arises from the decay of '72Hf. This isotope48 is made by the alpha irradiation of ytterbium [Yb(a,xn)' 72Hfl. The short-lived isotope of tantalum 178Ta has proved useful for cardiac imaging and a generator49 for its production (decay of 178W -z1,2 21.7d) has been described. The heavier isotope of tungsten Ig8W can be useds0 as the mother isotope in a new generator for '"Re. Methods for the production and purification of 1940s,parent isotope in the 1940s/'941r generator have been de~cribed.~' 191Pt can be made by the proton irradiation of natural irid- ium52 and a new heavy isotope of platinum 202Pt has been reported.53 When plati- num is irradiated with neutrons '99Au results,54 an isotope which can be used diagnos- ti~ally~~ in nuclear medicine.201T1 has similar applications and can be made by the proton irradiation of mercury thallium,56 or lead-204.s7 Whilst "Po arises naturally as part of the uranium decay chain it is more convenient to make it artifi~ially,~~ by the neutron irradiation of 'O'Bi. This isotope can also be used for the preparation of 211At [209Bi(a,2n)21 Lighter isotopes of astatine (208 209 and 210) are formed6' if 209Bi is bombarded with helium-3 nuclei. A method has been described for the prepara- tion for the first time,61 of pure 223Fr (decay of 227A~). Experimental details have been described for the purification of 223Ufrom thorium62 and of neptunium63 and plutonium64 from neutron-irradiated targets of 43 2.Mazgaj A. Kolaczkowski J. Mikulski A. F. Novgorodov and A. Zielinski Report 1505/c Inst. Nuclear Physics Cracow Poland 1990. 44 H. Tang J. Ding and Q. Lin J. Nuclear Radiochem. 1993 15 144. 45 (a)M. L. Firouzbakht D. J. Schlyer and A. P. Wolf,J.Labelled Compd. Radiopharm. 1993,32,243;(b)N. 1. Venikov V. I. Novikov and A. A. Sebiakin ibid. 1993 32 222; (c)N. V. Kurenkov A. B. Malinin A. A. Sebyakin and N.I. Venikov ibid. 1993 32 233. 46 V.N. Reddy G. S. Murthy and A. Dash Ref. 29(a) p. 412. 47 J. Zweit J. W. Babich and R.J. Ott J. Labelled Compd. Radiopharm. 1993 32 480. 48 S.K. Das and A. G. C. Nair Ref. 29(a) p. 436. 49 W. W.Layne and J.L. Lacy Ref. 18 p. 213. 50 G.A. Brodskaya and O.U. Gapurova Radiochemistry (New York) 1994 35 325 (Russian original Radiokhimiya 1993 35(3) 92). S. Mirzadeh D. E. Rice A. P. Callahan and F. F. Knapp Jr. J. Labelled Compd. Radiopharm. 1993,32 471. 52 A. M. B. Bittencourt Filha M. A. V. Bastos and J. A. Medeiros Ciencia e Cultura. Suplemento 1993,45500. 53 D. Yin Y. Li W. Huang and S. Shi Nuclear Techn. 1993 16 521. M. Akhtar A. Mushtaq H. M.A. Karim and M.A. Khan Radiochim. Acta 1994 64 137. 55 M. Bonardi F. Groppi G. Sanvito and M. Gallorini J. Labelled Compd. Radiopharm. 1993 32 483. 56 L. Fernandes S.T. 1. Yanagawa J. Mengatti C. Nakanishi and M. E. D. Acar Report 390 Inst. de Pesquisas Energeticas e Nucleares Slo Paulo Brazil 1993. 57 V.A. Ageev A. A. Klyuchnikov A. A. Odintsov A. D. Sazhenyuk V. N. Bukanov E.G. Vasil'eva and N. A. Shovkum Radiochemistry (New York) 1992 34 250 (Russian original Radiokhimiya 34(2) 122). 58 M.T. Azure and R. W. Howell Appl. Radiat. Isotopes 1994 45 637. 59 Z. Mazgaj and J. Mikulski Report 1610/c Inst. Nuclear Physics Cracow Poland 1992. 6o F. Szelecsenyi Z. Szuecs 0.Solin J. Bergman and S.-J. Heselius J. Labelled Cornpd. Radiopharrn. 1993 32 443. 61 Z. Szeglowski 0.Constantinescu M. Hussonnois A. Abdul-Hadi and G. J. Ardisson Radiochim. Acta 1994 64 57. 62 (a)M. Venkatesan S.V. Mohan T. N. Ravi R. Srinivasan V. R. Raman and G.R. Balasubramanian Ref. 29(a),p. 270; (b)C. I. Pius M. M. Charyulu A. V. Kadam and C. K. Sivaramarkrishnan Ref. 29(a),p. 117. 63 L.F.Bellido V.J. Robinson and H.E. Sims J. Radioanal. Nuclear Chem. 1993 172 107. 64 P. K. Mohapatra V. K. Manchanda and A. Ramaswami Ref. 29(a) p. 228. Rad iochemistry 503 uranium. The use of a crown ether in the organic layer enabled 235U to be preferentially extracted6' from aqueous solutions of uranyl chloride. Californium isotopes (245 and 246) are reported66 to be formed when 238U is bombarded with 12C ions. 3 Chemical Effects of Nuclear Transformations Solid State.-Much effort has been expended over many decades to determine the fate and chemistry of recoil atoms in crystal lattices. Usually the results of (n,y) reactions have been investigated by dissolving the crystals and determining the chemical nature of the labelled products.A further refinement has been to subject the crystal to a period of heating before dissolution-annealing. In some cases it was reported that yields would oscillate as the annealing proceeded but recent has failed to confirm this behaviour. It is remarkable that despite the number of compounds that have been irradiated there has been a sparsity of systematic programmes of study to elucidate fundamental reaction mechanisms in a logical way. A notable exception is that of Mueller,68 whose detailed studies of recoil processes in mixed crystals of complex octahedral halide anions continues (e.y. K2ReBr6-K2SnC16).69 Similarly the reactions of recoil ruthenium and recoil technetium in the same initial complex (ruthenocene7' or tris-bipyridineruthenium(I1) chloride7') can be compared by varying the irradiation (neutron for recoil Ru or gamma for recoil Tc) enabling specific mechanisms to be proposed.In a rather more conventional way work continues to ascertain the factors that control the fate of recoil bromine (as 80Br 80mBr and 82Br)72 in various bromates Sr,74 Sm and Y75) and iodine (1281)in iodates.76 Liquid State.-The charged-plate technique whereby recoil reactions take place in the presence of an electric field continues to help to determine the role of charged species in 'hot atom' chemistry. Recent studies of recoil bromine7 and iodine78 with aromatic substrates have shown that reactions of positive ions usually predominate. Miscellaneous.-The stereochemistry of a hot atom reaction in which the recoil species replaces another atom in a molecule has long fascinated chemists.Rack and his group continue79 to investigate the factors which can determine whether recoil chlorine (38Cl) will replace chlorine or fluorine with inversion or retention of configuration. Steric hindrance and atomic size have been shown to be important. Hot atom chemistry has a way of cropping up in odd places such as the chemical fate of plutonium in the 65 Y. Han W. Luo and S. Gao Chin. J. Nuclear Sci. Engineering 1993 13 58. 66 A. Ramaswami G. K. Gubbi J. N. Mathur R. J. Singh and M. S. Murali Ref. 29(a) p. 84. 67 H. Mueller J. Radioanal. Nuclear Chem. 1993 172 249. H. Mueller ihid. 1994 181 211. (cf. Ref. 4(b)). " H. Mueller Rudiochim. Acta 1993 62 189. 'O H. Matsue T. Sekine and K.Yoshihara ihid. 1993 63 179. 71 H. Shoji Y. Watanabe and N. Ikeda ibid. 1993 63 183. 72 R.S. Lokhande and V.G. Dedgaonkar J. Ind. Chem. SOC. 1992,69 122. 73 K. K. Sahu and D. Bhatta Radiochim. Acta 1994 64 67. 74 R.S. Lokhande Ref. 29(a) p. 108. 75 V.G. Dedgaonkar R.G. Apte and D.A. Bhagwat Ref. 29(a) p. 110. 76 R. Khare and S. P. Mishra Ref. 29(a) p. 86. 77 (a)S. P. Mishra and M. R. Zaman Ref. 29(a),p. 106; (b)S. P. Mishra and M. R. Zaman Ref. 29(a) p. 113. 78 S.P. Mishra N. P. Singh and M. R. Zaman lnd. J. Chem. Sect. A. 1994 33 170. 79 R. J. Meyer F. Roman R. B. Sharma R. A. Ferrieri and E. P. Rack Rudiochim. Acta 1993 62 181. 504 David S. Urch environment8’ and the reactions of 244Pu with interstellar diamond crystals” (if plutonium had been held in such crystals it would be possible to explain xenon isotope ratios).It is also of importance when the chemistry of the very heaviest elements is studied since the initial chemical reactions of the atoms of such elements are necessarily ‘hot’.82 4 Labelled Compounds New methods for the production of labelled compounds and the introduction of new isotopes for use in nuclear medicine continues to be a growth area.83 Greatest interest is centred on rapid methods for the incorporation of short lived positron emitting isotopes for imaging. Automation of such procedures is also receiving increasing attention. Another area of growth (and rightly so) is that of quality control,84 the testing of radiopharmaceutical products for radiochemical and medical purity.Tritium 3H.-Apart from conventional organic procedures in which a tritium labelled reagent is used tritium can be introduced into an organic compound in two main ways either by exchange or by addition to an unsaturated site. The exchange reaction can be initiated either by the use of tritiated water or tritium gas but in either case catalysts are often used and polymer supported catalysts have been shown to be especially Rhodium trichloride catalyst directs86 the exchange reaction to aromatic ortho-positions and to activated (6 +) hydrogen sites. Noble metal catalysts (often palladium based) have been used to in the preparation of tritium labelled heterocyclic bases (adenisine and thymidine derivatives). Directing the label to a specific site can most easily be achieved by the replacement of a labile group such as a halogen.However even in this reaction use is often made of palladium catalysts as in the preparation of labelled benzylic acid” or pyrethr~id~~ derivatives 19-C3H] cholesterol,90 cyfluthrin,” care~edilol,~~ and complex antipsychotic agents (CP-88059),93enzyme inhibitor^,^^ and retinoic acid receptors.95 80 1.0. Essien J. Radioanal. Nuclear Chem. 1994 178 165. 81 P. K. Kuroda Rudiochim. Acta 1993 62 27. 82 (a) D.C. Hoffman ihid. 1993 61 123; (h) M.K. Gober ‘Development and application of HPLC separations to study heavy ion reactions and chemical properties of the element 105’,Thesis Mainz Univ. Germany 1993. 83 M. J. Welch Abstract CHED22 207 meeting Amer.Chem. Soc. (San Diego) 1994. 84 P. Schmidt F.T. Lee and R. Lambrecht in ‘Proc. 1st Australian-Asian conference on radiation science and nuclear medicine’ Lucas Heights N.S.W. Australia 1993 p. 8. Australian Institute of Nuclear Science and Engineering. 85 J.R. Brewer J.R. Jones K. W.M. Lawrie D. Saunders and A. Simmonds ‘Tritiation of organic compounds by polymer-supported acid catalysts’ J. Labelled Compd. Radiopharm. 1994 34 391. 86 K. Oohashi and T. Seki J. Radiounul. Nuclear Chem. 1994 187 303. 87 (a)G. V. Sidorov and N. F. Myasoedov Biaorgunicheskaya Khimiya 1993,19 1220; (h)G. V. Sidorov and N. F. Myasoedov ibid. 1993 19 1215; (c) G. V. Sidorov and N. F. Myasoedov J. Labelled Compd. Radiopharm. 1994 34 353; (d) G. V. Sidorov and N. F. Myasoedov ibid.1994 34 339. 88 V. P. Shevchenko 1. Yu Nagaev and N. F. Myasoedov ‘Preparation of 3H-labeled benzilic acid derivatives’ Rudiochemistry 1994 35 574 (Russian original Radiokhimiya 1993 35(5) 97). nq B. Lath L. J. Greenfield and J. E. Casida J. Labelled Compd. Rudiopharm. 1993 33 613. 90 (a)V. P. Shevchenko I. Yu Nagaev A. V. Potapova and N. F. Myasoedov Rudiochemistry 1993,3518; (Russian original Radiokhimiya 1993 35 106). 91 U. Pleiss J. Roemer and R. Thomas J. Labelled Compd. Radiopharm. 1993 33 949. 92 S. G. Senderoff A. J. Villani S. W. Landvatter K. T. Games and J. R. Heys ihid. 1993 33 1091. 93 H. R. Howard K. D. Shenk T. A. Smolarek M. H. Marx J.H. Windels and R. W. Roth ihid. 1994 34 117. 94 A.Y.K. Chung J. W. Ryan W.E. Groves F.A.Valido and P. Berryer ibid. 1993 33 483. 95 M.I. Dawson P.D. Hobbs S. W. Rhee H. Morimoto and P.G. Williams ibid. 1993 33 633. Radiochemistry 505 Metallation can also be used to indicate the site for tritium exchange as in the replacement of potassium96 in the preparation of C3H]ibogaine. Another way of ensuring that the tritium label is in the desired location is to allow tritium gas to add to a double bond. The mechanism and kinetics of this reaction have been studied97 and the method used9' to prepare [17,18-3H]prostoglandin Ei. Palladium on charcoal catalyst was used in the preparation of labelled 4-amino-3- phenylbutanoic acid99 whilst the use of tris(triphenylphosphine)rhodium(I)chloride facilitated the partial reduction of a triple bond leading to the formation of labelled (E)-and (2)-4-aminobut-2-enoic acids.' O0 Catalytic hydrogenation has also been used to label biocompatible polymers,' O1 from acetylenic starting materials and in the preparation of C3H]proadifen from an allylic intermediate.' O2 A new and convenient method for the preparation of tritium from the reaction of sodium [3H]borohydride with cobalt(I1) chloride has been described.'03 As this reaction can be carried out on a small-scale in the laboratory it provides a very useful alternative source of tritium gas.Carbon (l 'C).-[' 'CIMethyl iodide remains one of the most versatile and useful reagents for the incorporation of carbon-1 1 into organic molecules. Recent examples include the preparation of ''C-labelled dopamine D-1 receptor ligands,' O4 epineph-rine,' O5 dapoxetine hydrochloride,'06 N-[11C-methyl]chlorophentermine,'07" meth-arn~hetarnine,"~~ prenorphine derivatives"' and 6-[11C]-D-glucose.1 O9 A significant increase in the radiochemical yield of [''C-methyl] anisole was recorded' lo when the reaction (methyl iodide plus phenol) was carried out in liquid ammonia near the critical point.Whilst ["Clcarbon dioxide can be used directly in many preparations (e.g. 1-[' 'C]polyhomoallylic fatty acids)"' it is also a source112 for labelled hydrogen cyanide and cyanogen bromide. The former can be used to make l-["C]-96 H.H. Seltzrnan D.F. Odear C. P. Laudernan F. I. Carroll and C. D. Wyrick ibid. 1994 34 367. 97 V.P. Shevchencko I. Yu Nagaev and N.F. Myasoedov Radiochemistry (New York) 1994 35 476 (Russian original Radiokhimiya 1993 35(4) 126).98 V. P. Shevchencko I. Yu Nagaev and N. F. Myasoedov Radiochemistry (New York) 1992 34 138 (Russian original Radiokhimiya 1992 34(1) 172). 99 R.K. Duke R.D. Allan C.A. Drew G.A.R. Johnston and K.N. Mewett J. Labelled Compd. Radiopharm. 1993 33 767. lo" R. K. Duke R.D. Allan C.A. Drew G.A. R. Johnston M. A. Long and C. Than ibid. 1993,33 527. J. C. Russell P. W. Stratford J. R. Jones and T.A. Vick ibid. 1993 33 957. T. Werner L. Gawell and S. B. Ross ibid. 1993 33 627. S. Malik M. Kenny G. Doss and J. Varghese ihid. 1994 34 471. lo4 (a) C. Halldin L. Farde P. Karlsson C.-G. Swahn H. Hall G. Sedvall C. Foged K. Hansen and F. Groenvald Nuclear Med. Biol. 1993,20,945;(b)R.F. Dannals J. Labelled Compd. Radiopharm. 1994,34 431. P. K. Chakraborty D. L. Gildersleeve D. M. Jewett S. A. Toorongian M. R. Kilbourn M. Schwaiger and D. M. Wieland Nuclear Med. Biol. 1993 20 939. lo6 E. Livni W. Satterlee and R. L. Robey ibid. 1994 21 669. lo' (a)H. Kizuka and D. R. Elrnaleh Nuclear Med. Biol. 1993,20,239; (h)M. Mizugaki T. Hishinuma and H. Nakarnura ibid. 1993 20 487. Io8 S. K. Luthra F. Brady D. R.Turton D. J. Brown K. Dowsett S. L. Waters and A.K. P. Jones Appl. Radiat. Isotopes 1994 45 857. Io9 (a)J. R. Grierson J. E. Biskupiak J. M. Link and K. A. Krohn Appl. Radiat. Isotopes 1993,44,1449;(b) J.R. Grierson J.E. Biskupiak J.M. Link J.H. Courter and K.A. Krohn J. Labelled Compd. Radiopharm. 1993 32 537. G. Jacobson K. E.Markides and B. Laangstroem Acta Chem. Scund. 1994 48 428. M.A. Channing and N. Sirnpson J. Labelled Compd. Radiopharm. 1993 33 541. 112 G. Westerberg and B. Laangstroern Acta Chem. Scand. 1993 41 974. 506 David S. Urch glucosamine,' l3 ['lC]oxalic acid' l4 (itself a useful intermediate) and [''Clbenzamide derivatives.' ' Labelled cyanogen bromide proved useful in the preparation1l6 of ["Clalbumin and ["Cltransferin. A new method for making [''Clphosgene has been described;'17 this compound can then be used"' in the preparation of labelled 2-thymine. ["Clnitromethane has been used to make a series of labelled amines,"' including [l-"Cldopamine. Nitrogen (13N).-Despite its short half-life there is still interest in the preparation of compounds labelled with nitrogen-13.The starting compound is usually [13N] ammonia for which improved production parameters have recently been reported.' 2o Methods for the incorporation of 13N into aminesI2' and polypeptides122 have been described. Oxygen ("O).-The shorter half-life of this isotope has greatly restricted its application as a label for radiopharmaceuticals. Even so the preparation of oxygen-15 labelled carbon monoxide carbon dioxide,' 23 and butan01'~~ have been reported. Fluorine ("F).-For the most part the labelling of a wide range of organic compounds for use in nuclear medicine procedures is accomplished by now standard methods. These can be exemplified by the techniques used to introduce '*F into dopamine derivatives. This can be achieved by nucleophilic substitution using labelled potassium fluoride and kryptofix 222 (dopamine D2);'25 by the location of the fluorine label at a specific site using regioselective demetallation (either tin 6[' 'Flfluor~dopamine~~~ or mercury 3-O-methyl-6[ ''F]flu~rodopa~~~); or by straightforward nucleophilic sub- stitution of a nitro group 6[18F]fluorodopamine.'28 The yield of labelled product in such a nucleophilic displacement reaction correlate^'^^ quite well with the 13C NMR chemical shift.Rapid and/or improved methods have been reported for the preparation of intermediates such as 4[' 'Flbromo-or i~do-benzene,'~~ cyclopropyl-4-[' 'F] fluorophenyl ket~ne,'~' ["F]fluoroacetone,' 32 4-['8F]fluorobenzylbromide,'33 and 113 J.-0. Thorell and E.S.Stone J. Labelled Compd. Radiopharm. 1993,32 586. l4 J.-0. Thorell S. Stone-Elander N. Elander ibid. 1993 33 995. Y. Anderson M. Bergstroem and B. Laangstroem Appl. Radiat. Isotopes 1994 45 707. G. Westerberg and B. Laangstroem ibid. 1994 45 773. 11' F.R. Dobbs M. Franceschini and T. J. Tewson J. Labelled Compd. Radiopharm. 1993 32 191. C. J. Steel G.D. Brown and K. Dowsett ibid. 1993 32 178. K.-0. Schoeps C. Halldin C.-G. Swahn P. Karlsson H. Hall L. Farde and K. Naagren Nuclear Med. Bio. 1993 20 669. M. S. Berridge and B. J. Landmeier Appl. Radiat. Isotopes 1993 44 1433. G.W. Kabalka M.M. Goodman J.F. Green R. Marks and D. Longford J. Labelled Compd. Radiopharm. 1993 32 165. P. Landais P. Waltz K. Rose R. E. Offord H. Tochon-Danguy P. Goethals and K.Strijckmans ibid. 1993 32 171. 123 R. Iwata and T. Ido ibid. 1993,32 454. lZ4 S. M. Moerlein G. G. Gaehle K. R. Lechner R. K. Bera and M. J. Welch ibid. 1993 32 162. F. Takao S. Sasaki M. Maeda T. Fukumura T. Tahara K. Masuda and Y. Ichiya ibid 1993,33 1108. 126 M. Namavari N. Satyamurthy and J. R. Barrio Abstract MED151 Ref. 83. 12' T. Chaly D. Bandyopadhyay R. Matacchien A. Belakhieff V. Dhawan S. Takikawa D. Margouleff and D. Eidelberg Appl. Radiat. Isotopes 1994 45 25. D. Yushin J. S. Fowler and A. P. Wolf J. Labelled Compd. Radiopharm. 1993 33 645. R. Rengan P. K. Chakraborty and M. R. Kilbourn ibid. 1993 33 563. R. Gail and H. H. Coenen Appl. Radiat. Isotopes 1994 45 105. W. R. Banks R. D. Borchert and H. Dahren ibid. 1994 45 75. 13' (a)L.Zheng and M. S. Berridge J.Labelled Compd. Radiopharm. 1993,32,296;(b)B. M. Kinsey and T. J. Tewson ibid. 1993 32 300. 133 (a)A. Majafi A. Peterson and C. A. Irvine Nuclear Med. Biol. 1993,20,401; (b)A. Najafi A. Peterson M. Buchsbaum S. O'Dell and F. Weihmuller ibid. 1993 20 549 Radiochemistry 507 ['8F]fluorocarboxylic acids' 34 which can be used in the production of complex radiopharmaceuticals. A new method has been described'35 for making ["F] fluoromethane which avoids the use of volatile iodomethane. The demetallation step is effected by the use of microwave radiation. Indeed microwaves have proved very popular of late in fluorine labelling procedures as in the preparation of ["F] fluoroderivatives of aporphine tetrali~~,'~~ morphine,'37 and 2[' 8F]fluorodeoxy-glucose.'38 Elements of Modest Mass.-Methods have been described for the preparation of 32P labelled phosphocholines' 39 and a range of 35Slabelled insecticide^'^^ (e.g.fenthion).Both 45Ti and 47Sc'4' have nuclear properties that make them attractive as chemotherapeutic agents and starting materials for future syntheses have been made at least for titanium,'42 e.g. labelled titatnium tetrachloride and butotitane. Anti- bodies,'43 and a-fet~protein'~~ have been labelled with 64Cuand 65Zn respectively. In these cases it would seem to be a matter of hope and faith that the 'labelled' protein is not altered by the labelling process. Rather more clearly defined is the situation in gallium (67Ga) labelled p~lyaminothiols'~~ where the gallium is nested within a polydentate ligand.An extension of this idea has been used in the synthesis'46 of 67Ga-defroxamine-dioxin. The incorporation of 77Br into p-bromospiroperidol has been re~0rted.l~~ 90Y is a pure /?-emitter and can be used both diagnostically and therapeutically. Methods for the 'direct' labelling of monoclonal antibodies with this isotope' 48,149 and also the development of polydentate ligands which can encapsulate 90Y and then be linked to such antibodies"* have been reported. Technetium (99"'Tc).-Technetium is probably the most popular isotope for radiopharmaceutical use at the present time. This popularity is partially due to the ease with which technetium can be incorporated into a very wide range of compounds by standard chemical methods.Recent progress was covered by a conference 'Topical Symposium on the Behaviour and Utilization of Technetium'.' 51 For the most part technetium is generated by the decay of 99Moin the form of the pertechnate(vI1) anion. This is then reduced (stannous chloride is widely used) and the lower valency 134 (a) S. Guhike H.H. Coenen and G. Stoecklin J. Labelled Compd. Radiopharm. 1993 32 108; (b) S. Guhike H. H. Coenen and G. Stoecklin Appl. Radiat. Isotopes 1994 45 715. 135 W.R. Banks M. R. Satter and H. Dahren ibid 1994 45 69. 136 S. Zijlstra T. J. de Groot L. P. Kok G. M. Visser and W. Vaalburg J. Org. Chem. 1993 58 1643. 13' S. Zijlstra T.J. de Groot G. M. Visser and W. Vaalburg J. Labelled Compd. Radiopharm. 1993,32,267. 13' R.Chirakal L. Girard G. Fimau and E. S. Garnett ibid. 1993 32 123. 139 H. P. Deigner and B. Fymys ibid. 1994 34 185. 14' M. Dias and R. Mornet ibid. 1994 34 73. 14' L. F. Mausner K.L. Kolsky R.C. Mease M. Chinol G. E. Meinken R. F. Straub S.C. Srivastava L. Pietrelli and Z. Steplewski ibid. 1993 32 388. 142 F. Oberdorfer B.K. Keppler Y. Zhou F. Helus and W. Maier-Borst ibid. 1993 32 441. 143 C. J. Anderson S. W. Schwarz P. A. Rocque M. J. Welch J. M. Connett L. W. Guo G. W. Philpott K. R. Zinn and C. F. Meares ibid. 1993 32 368. 144 I. L. Preiss Abstract NUCL22 Ref. 83 p. 1035. 14' C.S. John G. Minear R.K. Keast S. Kinuya and C.H. Paik Nuclear Med. Biol. 1993 20 217. Y. Fujibayashi Y. Takemura H. Taniuchi J. Konishi and A. Yokoyama J. Labelled Compd.Radiopharm. 1993 32 420. 14' Y. Huang and Y. Li Nuclear Techn. 1994,17 233. 14* J. Zhang Q. Lin X. Jin and J. Tian Chin. J. Nuclear Med. 1993 13 173. 149 2.Yang X. Jin H. Yu S. Bai S. Jiang Z. Mong L. Yang X. Wei and A. Tian J. Isotopes 1992,5 72. (a)J. K. Moran M. Li and C. F. Meares Abstract NUCL87 Ref. 83 p. 1051;(b)Y. Li C. Guang C. Ma and L. Jing J. Isotopes 1994 7 21. 51 Conference Report 'Topical Symposium on the behaviour and utilisation of technetium' Sendai Japan 1993 Radiochimica Acta 1993 63. 508 David S. Urch techentium incorporated into many complexes. Sulfur is adept at forming strong bonds to technetium and many new complexes with Tc-S bonds have been reported e.g. thioether~"~ and ~ysteine.''~ A range of mercapto-mono -di and -tri glycine complexes of pentavalent technetium has also been ~repared.'~~-l These com- 56 pounds can be used as renal imaging agents.Related complexes have also been prepared in which the techentium was complexed by nitrogen as well as sulfur'57 (using ligands such as N,N'-bis(mercaptoacetamido)ethylenediamine). The combination of sulfur and nitrogen has also been used'58 to prepare complexes of (TcO;) with 1,6-di(2-thienyl)-2,5-diazahexane, and similar ligands complexes which can be used as myocardium radiotracers. Radiopharmaceutical uses have also been found for TcV complexes of 2,3 dimercaptosuccinic acid.' 59 Further complexes of TcV have been prepared with fi-diketonate groups,16o amino acids,161 or ethylene diamine deriva- tives162 and in which the technetium is also triply bound to nitrogen.'63 Other ligands that have been used to prepare technetium radiopharmaceuticals have included hydroxamide,' 64 phosphine derivatives' 65 and phosphorus hydrazide.'66 When attempts are made to label various monoclonal antibodie~'~~ the bonding to the technetium is usually assumed to go via sulfur and nitrogen sites,168 although whether labelling always proceeds without perturbing the biological activity has been questioned. 169 Iodine (1231,1251,and 13'I).-The simplest method for labelling with radioactive iodine is by halogen exchange as in the preparation of 5[1231]iodonicotinamide'70 from the H.J. Pietzsch S. Seifert R. Syhre and H. Spies 'Ann. Report 92' ed. B. Johannsen Institute of Bioinorganic and Radiopharmaceutical Chemistry Research Centre Rossendorf Dresden Germany 1993 p.82. lS3 S. Mukherjee C. Sengupta J. Chatterjee P. Dobe and S. Banerjee Nuclear Med. Biol. 1993 20 413. 154 B. Johannsen B. Noll P. Leibnitz G. Reck S. Noll and H. Spies Radiochim. Acta 1993 63 133. 155 (a)J. Koemyei J. Toerkoe and J. Volford J.Radioanal. Nuclear Chem. 1994,186,189; (6)J. Koemyei J. Toerkoe J. Volford and F. Sztaricskai Magyar Kemiai Folyoirat 1994 100 189. G. Bormans B. Cleynhens P. Adriaens A. Verbruggen and M. de Roo J.Labelled Compd. Radiopharm.. 1993,33 1065. 15' S. Luo Z. Liu C. Zhang P. Zhao and Y. Fu J. Isotopes 1993 6 7. lSRN.C. Goomer P. V. Kulkarni A. Constantinescu P. Antich R. W. Parkey and J. R. Corbett Nuclear Med. Biol. 1994 21 657.IS9 (a)L. Lindemann C.Schuettler C. Neumann R. Michael S. Seifert and B. Johannsen Ref. 152 p. 41; (6) B. Noll H. J. Pietzsch H. Spies L. Dinkelborg B. Johannsen and W. Semmler Ref. 152 p. 100; (c) T. Hirano K. Tomiyoshi Y. Zhang T. Ishida T. Inoue and K. Endo Eur. J. Nuclear Med. 1994,21 82. 160 (a)A. Mutalib T. Sekine T. Omori and K. Yoshihara Ref. 151 p. 117; (6) A. Mutalib T. Sekine T. Omori and K. Yoshihara Ref. 151 p. 123; (c) A. Mutalib T. Sekine T. Omori and K. Yoshihara J. Radioanal. Nuclear Chem. 1994 178 311. A. Marchi R. Rossi L. Marvelli and V. Bertolasi Inorg. Chem. 1993 32 4673. T. Takayama T. Sekine and K. Yoshihara J. Radioanal. Nuclear Chem. 1993 176 325. V. Comazzi E. Bellande R. Pasqualini L. Ucelli A. Duatti and A. Marchi J.Labelled Compd. Radiopharm. 1993 32 10. 164 M. Nakayama H. Saigo and A. Koda Appl. Radiat. Isotopes 1994 45 735. ''' E. Deutsch Ref. 151 p. 195. 166 W.A. Volkert P.R. Singh K. K. Katti A. R. Ketring and K. V. Katti J. Labelled Compd. Radiopharm. 1993 32 15. 167 (a)T. Qu Y. Wu X. Wang Y. Liu Y. Ye and C. Wu Ref. 151 p. 209; (b)S.C. Archimandritis E. Belkas A. D. Varvarigou K. Cotsyfakis J. Malamitsi C. Proukakis G. Sivolapenko J.Zorzos and D. V. Skarlos. J. Labelled Compd. Radiopharm. 1994 34 323; (c) S. W. Schwarz C. J. Anderson P. A. Rocque M. J. Welch J. M. Connett G.W. Philpott and W. G. Li Nuclear Med. Biol. 1994,21,619; (d)G. L. Griffiths A. L. Jones H. J. Hansen and D. M. Goldenberg ibid. 1994 21 649. 16' M. Nakayama T. Terahara and R. Ikeda Appl.Radiat. Isotopes 1994 45 41. 169 E. John S. Wilder and M. L. Thakur Nuclear Med. Commun. 1994 15 24. 170 K. A. Bergstroem J. T. Kuikka H. Mussalo E. Laensimies S. Loetjoenen P. Penttilae and J. Hiltunen J. Labelled Compd. Radiopharm. 1993 33 593. Radiochemistry 509 corresponding bromo-compound. When this procedure was used to make o-[' 311] iodohippuric acid,I7' m-[' 'I]iodobenzylguanidine,' 72 and [1251]iodomazindol' 73 copper(1) was used as a catalyst in the presence of suitable reducing agents. Other procedures require the presence of an oxidizing agent such as 'iodo-gen' chloramine-T hydrogen peroxide or peracetic acid. In the case of recent reports for the preparation of 2['231]iodomelatonin'74 and [1251 311]iodotyrosine derivative^'^^ the relative merits of different oxidants have been evaluated.When chloramine-T is used labelled iodate ions can be formed.'76 This problem is presumably avoided when nitric acid is used as in the recently reported'77 preparation of 5-iodo-2'-deoxyuridine. The radio-iodine label can be directed to a specific site in a molecule by arranging for it to displace an organotin group (usually tributylstannyl) e.g. labelled iodo-caramiphen,' 78 aziridinyl 4-iodotamo~ifen'~~ and monoclonal antibodies' 8o via N-sucinimidyl4-methyl-3-(tri-n-butylstannyl) benzoate. This reaction is performed in the presence of an oxidizing agent chloramine-T for 1231and '251 iodouracils18' and ( -)-5-iodobenzovesamicol,' 82 iodo-gen for ['23T]iomazenil,183 peracetic acid for ['23]iododopamines'84 and hydrogen peroxide for 17a-[(E)-2-[ '251]iodoethenyl] androsta-4-6-dien- 17B-ol-3-one.' 85 This type of reaction has also been used to make labelled 2-iodo-4-(3-trifluoromethyl-3H-diazirin-3-yl)benyzlesters' 86 compounds which on photolysis generate carbenes.These carbenes insert into C-H bonds (in phospholipids for example) and bring the radioiodine with them. Rare Earth Elements.-Complexes of substituted nitrogen crown ethers with 153Gd,187153Sm and 166Ho'88 have been prepared and evaluated for their radiopharmaceutical potential. Rhenium (Ig6Re and lS8Re).-Since rhenium is very similar to technetium in its chemistry many of the techniques being used to produce rhenium-containing radiopharmaceuticals are the same as those used for technetium.Thus disulfide bridges in proteins and antibodies can be reduced to thi01s'~~ which can then bond to rhenium. Radioactive rhenium is most easily made as the per-rhenate anion and this is reduced with reagents such as stannous ~hloride"~ (see above for Tc). Lower valency ''I M. T. Al-Kolaly S. El-Bayoumy M. Raieh and A. El-Mothy J. Radioanal. Nuclear Chem. 1993,174,3. '12 J. Zhu W. Yao and J. Ma Nuclear Techn. 1993 16 695. E. Galinier J. E. Ombetta Y. Frangin J. C. Besnard D. D. Guilloteau and J. Mertens J. Labelled Compd. Radiopharm. 1994 34 487. D. du T. Rossouw and J.H. Langenhoven Appl. Radiat. Isotopes 1994 45 902. "'S. Li Y. Liu X. Lin S. Deng M. Li T. Zhu and G. Zhong Nuclear Techn. 1993 16 669. M. Szabo and G. Toth J.Radioanal. Nuclear Chem. 1993 176 169. "' M. A. Trivedi J. Labelled Compd. Radiopharm. 1993 33 607. '" D. W. McPherson F.F. Knapp Jr. and R. L. Hudkins ibid. 1994 34 239. 179 R. McCague and G. A. Potter 1994 ibid. 1994 34 291. P. K. Garg S. Garg and M. R. Zalutsky Nuclear Med. Bio. 1993 20 379. la' H. Dougan B. A. Rennie D. M. Lyster and S. L. Sacks Appl. Radiat. Isotopes 1994 45 795. ln2 M. E. Van Dort Y.-W. Jung D. L. Gildersleeve C. A. Hagen D. E. Kuhl and D. M. Wieland. Nuclear Med. Biol. 1993 20 929. Y. Zea-Ponce R. M. Baldwin S. S. Zoghbi and R. B. Innis Appl. Radiat. Isotopes 1994 45 63. H. Xiaoshu B. R. de Costa L. Kansam and D. Weinberger J. Labelled Compd. Rudiopharm. 1993 33 493. P. J. Diaz Cruz H. E. Smith B. J. Danzo J. A. Clanton and N.S. Mason ihid. 1993 33 853. 186 T. Weber Thesis Eidgenoessische Technische Hochschule Zurich Switzerland. 1994. IR7 K. Kumar K. Sukumaran C. A. Chang M. F. Tweedle and W.C. Eckelman J. Labelled Compd. Radiopharm. 1993 33 473. K. McMillan and T. Masterson Abstract TECH9 Ref. 83 p. 420. M.A. Majali Ref. 29(a) p. 298. "') M. A. Majali J. Radioanal. Nuclear Chem. 1993 170 471. 510 David S. Urch rhenium as oxorhenium(v) can form a series of complexes with thio1s''l and thio-acids.' 92 Heavy Elements.-An improved method for the preparation of trans-diamminedi-chloro[' 95"Pt]platinum(~~) A rather different type of 'labelling' has been rep~rted."~ has been described'94 for the incorporation of 212Pb into tobacco smoke aerosols. This should enable smoke clearance from the lungs to be monitored and human volunteers are being called for.Astatine ['"At] despite its short half-life can be used to label monoclonal antib~dies'~~,'~~ and can be directed to a specific site by replacement of an organotin group (see iodine above) N-succinimidyl-p[21 'At] astatobenzoate. 197 Automation in Labelling.-The short half-lives of the isotopes used in positron emission tomography for nuclear medicine have lead to a rapid growth in automated procedures' 98 for the incorporation of these isotopes into suitable compounds. A wide range of such techniques for the preparation and purification of labelled compounds is given in 'New trends in radiopharmaceutical synthesis quality assurance and regulatory control'.' '' More specific details for particular processes have been described for the use of ["C]methyl iodide in methylation2" and in the preparation of [I 'C]diprenorphine.'08~201Other 'robotic syntheses' have been used to prepare 6-[ '8F]fl~orodopa202 and 2-deoxy-2[18F]fluoro-~-glucose.203 Quality Control.-Whilst it is one thing to make (or have robots make) labelled compounds it is quite another to ensure that they are chemically pure radiochemi- cally pure and if for use as radiopharmaceuticals are free of traces of toxic impurities.Furthermore it is important to be able to establish the radiochemical integrity of a labelled compound after it has been stored for some time (the critical period could be minutes or months depending on the isotope). These topics are dealt with in some detail in reference 199 whilst specific aspects of quality control of radiopharmaceuticals in Japan204 and Germany205 have been discussed recently.A detailed study of auto-decomposition in [35S]-labelled amino acids has shown206 that 19' H. Spies T. Fietz and H. J. Pietzsch Ref. 152 p. 94. 192 H. Spies T. Fietz H. J. Pietzsch and D. Scheller Ref. 152 p. 103. 193 K. Kawai H. Maki Y. Nakano M. Akaboshi and W. Ehrlich Annual Reports Research Reactor Institute Kyoto University Japan 1992 25 78. 194 J. C. Strong D. A. Knight and A. Black Journal of Aerosol Science 1994 25 199. 19' D. S. Wilbur R. L. Vessella J. E. Stray D. K. Goffe K. A. Blouke and R. W. Atcher Nuclear Med. Bid.. 1993 20 917. 19' J. Jin S. Zhang M. Zhou and N.Liu J. Isotopes 1992 5 65. 19' R.H. Larsen S. P. Hassijell P. Hoff J. Alstad E. Olsen I.B. Vergote L.N. De Vos K. Nustad and J. Bjoergum J. Labelled Compd. Radiopharm. 1993 33 977. 19' G. Appleqvist C. Bohm H. Eriksson and S. Stone-Elander ibid. 1993 32 184. 199 'New trends in radiopharmaceutical synthesis quality assurance and regulatory control' ed. A. M. Emran. Plenum Press New York NY. USA 1991. 2oo R. Iwata C. Pascali M. Yuasa K. Yanai T. Takahashi and T. Ido J.Labelled Compd. Radiopharm. 1993. 32 148. S.K. Luthra S. Osman D.R. Turton V. Vaja K. Dowsett and F. Brady ibid. 1993 32 518. 202 G. Reddy M. Haeberle H.-F. Beer and A. Schubiger ibid. 1993 32 248. '03 (a)S. Dietrich-Wolber H. Knigge W. J. Obers F. Oberdorfer and W. Maier-Borst ibid. 1993,32 144; (b) M.Yu Kiselev D. V. Solov'ev and M. V. Korsakov Radiochemistry (New York) 1992,34,256 (Russian original Radiokhimiya 1992 34(2) 129). 204 'The 14th quality control survey for radioisotope in vitro tests in Japan 1992' Radioisotopes (Tokyo) 1993 42 1. 205 C. Decristoforo F. Chen and G. Riccabona Nukleamedizin 1993 32 144. 206 T. Kato K. Saito and N. Kurihara Appl. Radiat. Isotopes 1994 45 693. Radiochemistry 511 the pattern of labelled products formed is more closely mimicked by electron bombardment than by y-irradiation. Labelled iodine compounds are particularly sensitive to self-induced decomposition usually leading to free radioactive iodide anion as the main impurity (e.g. m-[l3']-iodobenzylg~anidine~~~). Other aspects of quality control concentrate mainly on the detection of trace impurities of other isotopes as in the case of 67Ga (65Zn and 68Ga)208 or 201T1 (200T1 202T1 and 203Hg),209or of chemical contaminants such as tin (Sn" or SnIV) in technetium preparations.21O 5 Environment The environmental aspects of the use of radiochemicals in power generation,21' in hospitals and in research are the subject of ever increasing attention (and about time too!).It is of course not all man made. Radon has been with us for some time so that an up-to-date bibliography212 will be quite useful. Technetium on the other hand has as you might say been resurrected recently and all aspects of its use and environmental impact have been reviewed.213 The greatest concern is however associated with the nuclear industry and its waste products.The European Community has undertaken large-scale research projects on specific aspects of the problem such as the ways in which radio-colloids would be carried by gr~undwater~'~ and the complexes that the various actinide ions might form with 'humic acid'.215 Specific aspects of the latter problem have also been reported for curium americium,2 l6 and neptunium2 ' as well as for actinide ions in general.218 The ways in which radioactive isotopes (usually fission products) might interact with different soil types and minerals219 has been the subject of many investigations. How for example might "Sr l'omAg,or 134Cs be incorporated220 into plants grown in the Mediterranean region in sandy-loam soils? Similarly the sorption of radioiodine by clays 'rich-soil' and alumina,221 the adsorption of radium by a range of minerals,222 the adsorption of lead and bismuth '07 (a) A.R. Wafelman J.H. Baijnen C.A. Hoefnagel and R.A. A. Maes ibid. 1994 45 183; (b) A. R. Wafelman R. Suchi C. A. Heofnagel and J. H. Beijnen Eur. J. Nuclear Med. 1993 20 614. P. Szentgyoergyi F. Rakias and E. Bodor Itd. Izotoptechnika Diagnosztika 1992 35 103. 209 L. Fernandes and C. P.G. da Silva J. Radioanal. Nuclear Chem. 1993,172 313. 'lo M. A.T. M. de Almeida and C. P. G. da Silva ibid. 1993 176 225. 'I1 Z. Yoshida and S. Kihara Denki Kagaku Oyobi Kogyo Butsuri Kagaku 1994 62 8. 212 E. Bujdoso J. Radioanal. Nuclear Chem. 1993 171 501. '13 K.H. Lieser Radiochim. Acta 1993 63 5.214 J. I. Kim B. Delakowitz P. Zeh,T. Probst X. Lin U. Ehrlicher,C. Schauer M. Ivanovich G. Longworth S. E. Hasler M. Gardiner P. Fritz D. Klotz D. Lazik M. Wolf S. Geyer J. L. Alexander D. Read and J. B. Thomas 'Colloid migration in groundwaters Geochemical interactions of radionuclides with natural colloids' Progress Reports Comm. Europ. Comm. Bruxelles Belgium and Tech. Univ. Muenchen Garching Germany 1993-94. J.I. Kim G. Buckau R. Klenze D. S. Rhee H. Wimmer P. Decambox P. Mauchien C. Moulin V. Moulin J. Tits C. Marquardt J. Riegel P. Sattelberger G. Herrmann N. Trautmann A. Diercks J. Vancluysen A. Maes G. Bidoglio and L. Righetto 'Effect of humic substances on the migration of radionuclides Complexation of actinides with humic substances' Progress Reports Comm.Europ. Comm. Bruxelles Belgium and Tech. Univ. Muenchen Garching Germany 1992 and 1993. 'I6 J.I. Kim D. S. Rhee H. Wimmer G. Buckau and R. Klenze Rudiochim. Acta 1993 62 35. '17 S.K. Jha and I.S. Bhat Ref. 29(a) p. 446. 218 E. Tipping Radiochim. Acta 1993 62 141. 219 S. Ahmed A. Mannan F. Naheed M. Daud and I.H. Qureshi in 'Modern Trends in Contemporary Chemistry' ed. H. Javed H. Pervez and R. Qadeer Pakistan Atomic Energy Commission Islamabad Pakistan 1993 89. 220 M. Vidal and G. Rauret J. Radioanal. Nuclear Chem. 1994 181 85. 221 S. Assemi and H.N. Erten ibid. 1994 178 193. 222 R. S. Wang F. Liu H. Cheng P. Nar A.S.Y. Chau X. M. Chen and Q.Y. Wu ibid. 1993 171 347. 512 David S. Urch isotopes223 and uranyl cations224 by montmorillonite and of 6oCo and 134Cs by shales,225 have all been investigated recently.The council of perfection would of course be that radioactive isotopes fission or actinide did not enter the environment at all and so another important line of research is to investigate the ways in which such isotopes can be taken from solution at source. Many impurities can be removed by crown ethers (alkali and alkaline earth ions,226 stronti~m~~~-~~’ ,and also lanthanides and actinides229) or by triphenylphosphine oxide.230 Other techniques have concentrated on the use of heterogeneous adsorption by alumina,231 by iron hydroxide (uranium,232 60C0233) or by manganese diox- ide(133Ba and 210Pb).234 Silica gel coated with ‘Versatic-10’ is reported235 to extract Uvl quantitatively from solution.51Cr and 125Sb can be removed from the liquid wastes from a pressurized water reactor by membranes impregnated with titania and zirconium phosphate.236 The use of polyamine ion exchange resins has been advocated237for the chelation of specific isotopes e.y. IB5W,99M0 and 125Sb7 by suitable modification conditions for the preferential extraction of individual elements. Some radioactive impurities are gaseous and in the case of tritium special alloys have been developed238 to adsorb it. Rather more of a problem is when tritium becomes adsorbed not as part of some recovery-purification programme but on building materials239 such as concrete. The final environmental problem (in many senses of the word) is the ‘disposal’ i.e. containment of long-lived nuclear waste.Glass is widely favoured as a possible encapsulant but for how long240 and what of changes in local pH?241 Groundwater circulating near such glasses (at 9OOC) might well become contaminated with radio-c~lloids~~~ and if the solutions are rich in salt further complications can 223 H.J. Ulrich and C. Degueldre Radiochim. Acta 1993 62 81. 224 R. A. Matzner J. M. Berg C. J. Chisholm-Brause and D. E. Morris Abstract ENVR229 Ref. 83 p. 586. 225 H.A. Einaggar M.K. Shehata M.F. Abdelsabour and M.R. Ezzeldin in ‘Proc. 5th Conference on Nuclear Sciences and Applications’ The Egyptian Society of Nuclear Sciences and Applications Cairo Egypt 1992 2 999. 226 V.V. Yakshin and O.M. Vilkova Radiochemistry (New York) 1993 35 58 (Russian original Radiokhimiya 1993 35(1) 80).227 F.A. Shehata S. H. Khalifa and H. F. Aly Ref. 225 3 389. 228 L. He X. Wong D. Yang R. Jiao and C. Song Report 00744 China Nuclear Information Centre Beijing China 1993. 229 R. Shu H. Zhao J. Hu and H. Huang Atomic Energy Sci. Techn. 1993 27 242. 230 Y. Zhu J. Tsinghua University. Sci. Techn. 1992 32 1. 231 G. Bernhard J. Radioanal. Nuclear Chem. 1994 177 321. 232 Y. Ye G. Marx and Ch. Keiling J. Nuclear Radiochem. 1993 15 134. 233 M.M. Bhutani K. Ramesh and S. Agarwal Ref. 29(a) p. 305. 234 D. Tait G. Haase and A. Wiechen J. Radioanal. Nuclear Chem. 1994 186. 235 U.S. Ray and K. Mitra Ref. 29(a) p. 294. 236 E.W. Hooper and P. Kavanagh Proc. Int. Conference. ‘Water Chemistry of Nuclear Reactors’ British Nuclear Energy Society London UK 1992 p.228. 237 S. C. Gupta B.B. Tak N. K. Mathur and C.K. Narang J. Radioanal. Nuclear Chem. 1993 170 3. ”’ M. Kitamura and S. Yamashita Japan Patent 5-341096/A. 1993. 239 (a)R. S. Dickson and J. M. Miller Report G91114 Canadian Fusion Fuels Technology Project Atomic Energy of Canada Ltd. Chalk River Ont. Canada 1991; (b)J. M. Miller J. A. Senohrabek and P. A. Allsop Report (39198 Canadian Fusion Fuels Technology Project Atomic Energy of Canada Ltd. Chalk River Ont. Canada 1992. 24” W. L. Ebert J. K. Bates C. R. Bradley E. C. Buck N. L. Dietz and N. R. Brown ‘Ceramic Transactions Environmental and Waste Management Issues in the Ceramic Industry’ ed. G. B. Mellinger American Ceramic Society 1994 39 333. 241 D. Oksoy L.D. Pye D. F. Bickford and W.G. Ramsey ibid. p. 365. 242 X. Feng E.C. Buck C. Mertz J. K. Bates J. C. Cunnane and D. Chaiko Report CP-78677 Argonne National Lab. Illinois USA 1993. Radiochemistry arise243 (for uranium244 and plutonium245). 6 Miscellaneous Standards.-The development of standard uranium samples for use with the isotope dilution method has been reported246 as well as the preparation of 45Ca for liquid scintillation counting. Tritium.-The thermodynamic properties of ditritium i.e. pressure-volume relation- ships as a function of temperature have been as have the diffusion coefficients for 3H.’H (and 2H2 and 1H2)249 in various zeolites. It has been found250 that the UV-induced oxidation of gaseous ditritium is enhanced by the presence of carbon tetrachloride.Some new patents have indicated how tritium may be incorporated into aerogels2’ ’ and into solid radioluminescent light so~rces.~ 52 Various.-‘Technegas’ has been shown2 53 to contain fullerene (C,,) type molecules harbouring a 99mTc atom within the cage. Thin films of ’7C0 and 59C0 can be laid on stainless steel foils electrochemically. The technique of thermochromatog- raphy when applied to volatile hexafluororacetylacetonates allows25’ an efficient separation of the elements present in ‘natural’ uranium. Dating.-The problems associated with the dating of aquifiers by 14C2’6 or for older structures by 36Cl or 4He (from uranium decay) have been critically examined257 and an improved method for the dating ofgypsum and anhydrite has been reported.258 The role played by technetium in natural nuclear reactors such as that at Okl~,~’~ and in estimating the age of the solar system has been described.260 243 Yu.M.Rogozin E.A. Smirnova V.G. Savonenkov A.S. Krivokhatskii V.A. Avdeev and E.Yu. Sagaidachenko Radiochemistry (New York) 1993 35 124 (Russian original Radiokhimiya 1993 35(1) 166). 244 P. M. Heppner Report BMFT 02U5998 Freie Univ. Berlin Germany 1992. 24s I. Pashalidis and J. I. Kim Report BMFT 02U5958 Technische Univ. Miinchen Garching Germany 1992. 246 (a) M. V. Ryzhinskij M. Yu. Vitinskij and A. V. Lovtsyus Radiokhimiya 1993 35(5) 104; (b)M. Yu. Vitinskij M. V. Ryzhinskij A. V. Lovtsyus and L. F. Solntseva ibid. 1993 35 112. 247 L. Rodriguez Barquero J.M.Los Arcos Merino and A. Malonda Grau Report 719 Centro de lnvestigaciones Energeticas Medioambientales y Tecnologicas Madrid Spain 1994. 248 E. R. Grilly J. Res. National Institute Standards Techn. 1993 98 679. 249 A. S. Polevoi Radiochemistry (New York) 1994 35(5) 609 (Russian original Radiokhimiya 1994 35(5) 138). 250 K. Hasegawa H. Fusumae S. Miyahara and M. Shinohara Toyama Daigaku Suiso Doitai Kino Kenkyu Senta Kenkyu Hokoku 1993 12 85. 251 G. A. Jensen D. A. Nelson and P. M. Molton US. Patent 5,100968/A Patent and Trademark Office Washington USA 1992. 252 C. S. Ashley C. J. Brinker S. Reed and R. J. Walko US. Patent 5,240,647/A Patent and Trademark Office Washington USA 1993. 2s3 D. W. J. Mackey W. M. Burch I. G Dance K. J. Fisher and G.D. Willett Nuclear Med. Commun. 1994 15(6) 430. 254 R. Gonzalez-Rimirez H. Jimenez-Dominiquez E. Ordonez-Regil A. Cabral-Prieto and S. Bulbulian J. Radioanal. Nuclear Chem. 1993 174 291. 255 E. V. Fedoseev S. S. Travnikov P. A. Korovaikov A. V. Davydov and B. F. Myasoedov Radiokhirniya 1993 35(5) 57. 2s6 P.K. Bishop P.C. Smalley D. Emery and J.A.D. Dickson J. Hydrology 1994 154 301. 257 E. Mazor ibid. 1994 154 409. 258 J. A. Fitzpatrick and J. L. Bischoff Radiochim. Acta 1994 64 75. 259 H. Hidaka K. Shinotsuka and P. Holliger ibid. 1993 63 19. P. K. Kuroda ibid. 1993 63 9.