166Ho and 90Y labeled 6D2 monoclonal antibody for targeted radiotherapy of melanoma: comparison with 188Re radiolabel

166Ho 和 90Y 标记 6D2 单克隆抗体用于黑色素瘤靶向放射治疗:与 188Re 放射性标记物的比较

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作者:S Thompson, B Ballard, Z Jiang, E Revskaya, N Sisay, W H Miller, C S Cutler, E Dadachova, L C Francesconi

Conclusions

(166)Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the (90)Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. We concluded that the serum half-life of the 6D2 carrier antibody matched well the physical half-life of (166)Ho to deliver the tumoricidal absorbed dose to the tumor. Further investigation of this radionuclide for RIT of melanoma is warranted.

Methods

6D2 was radiolabeled with longer lived β emitters (90)Y and (166)Ho in treatment of experimental melanoma in A2058 melanoma tumor-bearing nude mice. The immunoreactivity of the radiolabeled 6D2 mAb, its in vitro binding to the MNT1 human melanoma cells, the biodistribution and therapy in A2058 human melanoma bearing nude mice as well as dosimetry calculations were performed.

Results

When labeled with the longer lived (90)Y radionuclide, the 6D2 mAb did not produce any therapeutic effect in tumor bearing mice while the reduction of the tumor growth by (166)Ho-6D2 was very similar to the previously reported therapy results for (188)Re-6D2. In addition, (166)Ho-labeled mAb produced the therapeutic effect on the tumor without any toxic effects while the administration of the (90)Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. Conclusions: (166)Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the (90)Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. We concluded that the serum half-life of the 6D2 carrier antibody matched well the physical half-life of (166)Ho to deliver the tumoricidal absorbed dose to the tumor. Further investigation of this radionuclide for RIT of melanoma is warranted.

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