"Targeted Ac-225-radiopharmaceutical for metastatic uveal melanoma"Period of Performance: 9/18/2017 - 9/17/2019

黑素皮质素1受体(MC1R)在葡萄膜和皮肤黑色素瘤细胞上高度表达，而在任何引起毒性的组织上都不表达。我们开发了一种专有的配体(MC1RL)，它与黑色素瘤细胞具有高亲和力和特异性。我们最近完成的SBIR第一阶段合同结果显示，在动物模型中，AC-225-DOTA-AHX-MC1RL的剂量没有明显的毒性，对葡萄膜和皮肤黑色素瘤产生了突出的疗效。生物分布、放射剂量测定和PK研究也显示血液清除迅速，主要分布到靶肿瘤或清除器官，没有器官特异性病理。这些结果非常支持人类候选药物治疗转移性黑色素瘤的可能商业化。

Melanocortin 1 receptor (MC1R) is highly expressed on uveal and cutaneous melanoma cells and not on any tissues that are of concern for causing toxicity. We developed a proprietary ligand (MC1RL) that binds to melanoma cells with high affinity and specificity. Our recently completed SBIR Phase I contract results show no overt toxicity at dosages of Ac-225-DOTA-Ahx-MC1RL that produce outstanding efficacy against uveal and cutaneous melanoma in animal models. Biodistribution, radiodosimetry, and PK studies also show rapid blood clearance with predominant distribution to the targeted tumor or to clearance organs with no organ specific pathology. These results are very supportive of possible commercialization of a human drug candidate for the treatment of metastatic melanoma.