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

• Published in: Nuclear medicine and biology 2014-03, Vol.41 (3), p.276-281
• Main Authors: Thompson, S., Ballard, B., Jiang, Z., Revskaya, E., Sisay, N., Miller, W.H., Cutler, C.S., Dadachova, E., Francesconi, L.C.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibody; Cell Line, Tumor; Drug Stability; Female; Half-Life; Holmium; Humans; Melanoma; Melanoma, Experimental - pathology; Melanoma, Experimental - radiotherapy; Mice; Mice, Nude; Pentetic Acid - chemistry; Radioimmunotherapy - methods; Radioisotopes; Radiotherapy; Tissue Distribution; Yttrium Radioisotopes
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2013.12.015

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 (Emax>1.5MeV) emission properties. 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. 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. 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.