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

Introduction: An approach to radioimmunotherapy (RIT) of metastatic melanoma is the targeting of melanin pigment with monoclonal antibodies (mAbs) to melanin radiolabeled with therapeutic radionuclides. The proof of principle experiments were performed using a melanin-binding antibody 6D2 of IgM isotype radiolabeled with a β emitter ¹⁸⁸Re and demonstrated the inhibition of tumor growth. In this study we investigated the efficacy of 6D2 antibody radiolabeled with two other longer lived β emitters ⁹⁰Y and ¹⁶⁶Ho in treatment of experimental melanoma, with the objective to find a possible correlation between the efficacy and half-life of the radioisotopes which possess high energy β (E_max>1.5MeV) emission properties. Methods: 6D2 was radiolabeled with longer lived β emitters ⁹⁰Y and ¹⁶⁶Ho 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 ⁹⁰Y radionuclide, the 6D2 mAb did not produce any therapeutic effect in tumor bearing mice while the reduction of the tumor growth by ¹⁶⁶Ho-6D2 was very similar to the previously reported therapy results for ¹⁸⁸Re-6D2. In addition, ¹⁶⁶Ho-labeled mAb produced the therapeutic effect on the tumor without any toxic effects while the administration of the ⁹⁰Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. Conclusions: ¹⁶⁶Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the ⁹⁰Y-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 ¹⁶⁶Ho to deliver the tumoricidal absorbed dose to the tumor. Further investigation of this radionuclide for RIT of melanoma is warranted.