Purpose: The radionuclide 186Re has favorable physical characteristics for use in radioimmunotherapy, including the emission of β- particles of a high-energy and a low-abundance of γ-emission. The γ- emission, in particular, is ideal for tumor imaging and poses less hazards to the patient and the medical personnel when compared with the γ-emission of the widely used radionuclide 131I. In the present study, we determined whether 186Re-labeled monoclonal antibody 323/A3 may be better suited for the treatment of ovarian cancer than 131I-323/A3. Methods and Materials: We compared the biodistribution and the efficacy of 186Re- and 131I- labeled 323/A3 in nude mice bearing s.c. the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. 186Re was conjugated to 323/A3 with the use of the S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3) chelate. Results: A molar ratio of Re-MAG3:323/A3 of 3:1 did not affect the integrity and the pharmacokinetic behaviour of the MAb. The tumor uptake and the retention of 186Re- and 131I-labeled 323/A3 were comparable, but the cumulative absorbed radiation dose in the tumor delivered by 186Re-323/A3 was 1.3- fold higher than that of 131I-323/A3. When mice were treated with equivalent radionuclide doses, the tumor growth inhibition induced by 186Re-323/A3 was similar or slightly better when compared with the efficacy of 131I-323/A3. When mice were treated with radionuclide doses that were adjusted to obtain equal cumulative absorbed radiation doses in the tumor for both conjugates, 131I-323/A3 was slightly more effective in the inhibition of the growth of FMa and OVCAR-3 xenografts. Conclusions: The favorable physical characteristics of 186Re as well as its efficacy when conjugated to a MAb indicate 186Re as an attractive radionuclide in radioimmunotherapy of ovarian cancer patients.
|Number of pages||11|
|Journal||International Journal of Radiation Oncology Biology Physics|
|Publication status||Published - 1 Jul 1997|