كاربرد آنتي بادي هاي نشاندار با مواد راديو ايزوتوپ براي آلفاتراپي سرطان

Targeted alpha therapy using radiolabeling of monoclonal antibody

Effective radiotherapy requires high selectivity and cytotoxicity. An alpha emitting radio-immunoconjugate (RIC) was prepared and tested against malignant melanoma. The melanoma monoclonal antibody 9.2.27 was labeled with an alpha emitter, Bismuth-213 and a positron emitter, Terbium-152. Two-chelator agents cDTPAa (cyclic anhydride of diethylene triamine pentaacetic acid) and a DTPA derivative, CHX-A (2-[p-isothiocyanatobenzyl]-cyclohexyl), were used to obtain high labeling yields for both radioisotopes. The labeling efficiency with 213Bi was found to be 96% and 92% for cDTPAa and CHX-A respectively. With 152Tb, it was 93% and 89% respectively. Serum stability studies showed a maximum of 20% and 13% leaching for 213Bi and 152Tb respectively. Cell avidity studies showed no difference in cell-binding of the labeled and unlabeled antibodies. Cell survival data indicated that the therapeutic activity ratio with both radioisotopes for same endpoint (Do) was 120. The high stability and outstanding cytotoxicity of the alpha emitter, offers a new approach to the control of metastatic melanoma.