摘要:

Trials of radiolabeled antibody therapy in patients with B‐cell lymphoma have been the most promising of any in radioimmunotherapy. Response rates of greater than 90% with many complete remissions have been reported by several groups using either low (185–370 MBq) or high (8.6–22.5 GBq) doses of I‐131‐labeled antibodies against B‐cell antigens. Estimated doses delivered to normal organs have ranged from 0.2 to 2.2 mGy/MBq and have shown similar interpatient variation in all series, despite differences in antibody specificity and dosimetric techniques. Tumor doses have ranged from 0.5 to 5.4 mGy/MBq. There has been little correlation of tumor response with estimated tumor dose. Toxicity has been limited to bone marrow suppression which has been greater with the higher amounts of I‐131. An advantage for a particular antibody specificity or for high dose compared to multiple low doses has yet to be demonstrated.

ISSN:0269-3127    

DOI:10.1118/1.597052

出版商:American Association of Physicists in Medicine    

年代:1998

数据来源: WILEY

摘要:

Dosimetry data arising from a decade of radioimmunotherapy are summarized along with techniques utilized to arrive at the reported dose estimates. Generality of the MIRD methodology allows it to serve as a vehicle for the calculation of solid tumor dosimetry although several limitations exist. Nonstandard geometries of solid tumors will ultimately necessitate determination of absorbed fractions for the individual tumors. Several approaches currently under investigation are described. For reasons of practicality, solid tumor dosimetry estimates continue to use the assumption of homogeneous activity distribution in a source organ, accounting for either all radiation or only nonpenetrating radiation. As computation tools become available for incorporating inhomogeneous cellular level data, the currently used “average dose” as an index of tumor sterilization will likely be replaced with a statistical distribution based on the number of viable cells in the tumor volume. Estimates of a tumor control dose would be based upon a linear extension of dose coupled with a threshold dose for cell sterilization.

ISSN:0269-3127    

DOI:10.1118/1.597053

出版商:American Association of Physicists in Medicine    

年代:1998

数据来源: WILEY

摘要:

Intraperitoneal and intracavitary radioimmunotherapy differ from other approaches of radioimmunotherapy in that high activity and dose gradients exist near the solution/tumor interface. Dose to tumor and normal tissue at the interface is a function of depth and is due to three major components: (1) the activity concentration of the administered radiolabeled antibody solution as a function of time within the compartment; (2) the spatial distribution of antibody/radionuclide complex as a function of depth and time as the biomolecules bind to and permeate tumor/normal tissues; and (3) the physical characteristics of the radionuclide in relation to depth of antibody penetration. In this review, the biological and physical aspects of intraperitoneally administered radiolabeled antibodies are discussed, and the state of experimental and calculational studies for this site is described. Areas requiring future investigation are examined, and recommendations are made regarding the type of measurements and calculations which are required for accurate dosimetry.

ISSN:0269-3127    

DOI:10.1118/1.597054

出版商:American Association of Physicists in Medicine    

年代:1998

数据来源: WILEY

摘要:

This paper reviews the radiobiological aspects of radioimmunotherapy (RIT) with radiolabeled antibodies, including comparisons between RIT and external beam irradiation. The effectiveness of cell killing by radiation decreases with the dose rate and the rate of decrease is determined by the size of the shoulder on the radiation survival curve. Tumors with poor repair capabilities exhibit less of a dose rate effect than tumors with good repair capabilities. Continued tumor cell proliferation during treatment occurs at very low dose rates and can contribute to the reduced effectiveness of low dose rate radiation. Toxicity to normal tissues will determine the total dose of radiolabeled antibody that can be given and this will be influenced by the choice of both the radionuclide and the antibody. The reported enhanced effectiveness of RIT may be due to multiple factors including selective targeting of cells responsible for tumor volume doubling, tumor surface binding rather than homogeneous binding throughout the tumor volume, targeting of the tumor vasculature, or block of cell cycle progression inG2. During RIT, there is less time for reoxygenation of hypoxic tumor cells than during a course of conventional external beam radiotherapy. It has not yet been determined whether this will have a detrimental effect on RIT. Probably the most important factor in the success of RIT is dose heterogeneity. Any viable portion of a tumor that is not targeted and does not receive a significant radiation dose will potentially lead to treatment failure, no matter how high the dose received by the remainder of the tumor. Comparisons between RIT and external beam radiation have shown a wide range of relative efficacy. Tumors most likely to respond to RIT are tumors with poor repair capabilities, tumors that are susceptible to blockage in radiosensitive phases of the cell cycle, tumors that reoxygenate rapidly, and tumors that express the relevant antigen homogeneously. From a radiobiological perspective, it appears that RIT alone is unlikely to cure many tumors and that combination with other treatment modalities will be essential.

ISSN:0269-3127    

DOI:10.1118/1.597055

出版商:American Association of Physicists in Medicine    

年代:1998

数据来源: WILEY

ISSN:0269-3127    

DOI:10.1002/j.2473-4209.1993.tb00068.x

出版商:American Association of Physicists in Medicine    

年代:1998

数据来源: WILEY