SBIR PHASE I-RADIONUCLIDE THERAPY FOR METASTATIC MELANOMA VIEWPOINT MOLECULAR TARGETING, LLC:1256544 [15-068338] IGF::OT::IGF

转移性黑色素瘤由于对所有治疗产生耐药性而几乎一律是致命的。而 最近FDA批准的药物正在取得轰动效应（blockbuster）地位（例如，Zelboraf），预期寿命增加 只有几个月而且副作用很严重虽然放射性核素治疗的商业潜力得到了证明， 通过最近的引入（例如，Xofigo），该方法尚未引入转移性黑色素瘤。在这 根据这项建议，我们确定了一种新的联合图像引导放射性核素治疗转移性肝癌的可行性。 使用我们的新[203/212 Pb]标记产品（DOTA-VMT-MCR 1和DOTA-RMX-GC）治疗黑色素瘤， 黑色素瘤特异性分子靶标具有高亲和力和特异性。在研究中，我们将 确定DOTA-VMT-MCR 1/DOTA-RMX-GC作为单独配体和多受体的商业可行性， 同时靶向MCR 1/GLUT的靶向混合物用于图像引导的放射性核素治疗。的 第一阶段SBIR的目的是：（1）确定放射合成[212 Pb]DOTA-RMX-GC的可行性 和[212 Pb]DOTA-VMT-MCR 1，使用两个可用的212 Pb发生器;（2）评估[212 Pb]DOTARMX的可行性- GC和[212 Pb]DOTA-VMT-MCR 1治疗荷黑色素瘤小鼠;和（3）确定 双靶向（GLUT 1/MCR 1）生物缀合物用于放射性核素成像和转移性肿瘤治疗的可行性 黑素瘤随着这些目标的成功，我们希望通过降低风险来推进我们的化合物 新药申请和临床试验的里程碑。

Metastatic melanoma is almost uniformly fatal due to the development of resistance to all treatments. While recent FDA-approved drugs are achieving blockbuster status (e.g., Zelboraf), life expectancy is increased by just months and side effects are severe. While the commercial potential of radionuclide therapy is evidenced by recent introductions (e.g., Xofigo), the approach has yet to be introduced for metastatic melanoma. In this proposal, we determine the feasibility of a novel combination image-guided radionuclide therapy for metastatic melanoma using our new [203/212Pb]-labeled products (DOTA-VMT-MCR1 and DOTA-RMX-GC), which target melanoma specific molecular targets with high affinity and specificity. In the proposed research, we will determine the commercial feasibility DOTA-VMT-MCR1/DOTA-RMX-GC as separate ligands and as multireceptor- targeted hybrids that target MCR1/GLUT simultaneously for image-guided radionuclide therapy. The objective of this Phase I SBIR is to: (1) Determine the feasibility of radiosynthesis of [212Pb]DOTA-RMX-GC and [212Pb]DOTA-VMT-MCR1 using two available 212Pb generators; (2) Evaluate the feasibility of [212Pb]DOTARMX- GC and [212Pb]DOTA-VMT-MCR1 therapy in melanoma-tumor-bearing mice; and (3) Determine the feasibility of a dual-targeted (GLUT1/MCR1) bioconjugate for radionuclide imaging and therapy for metastatic melanoma. With success in these aims, we expect to advance our compounds through risk-mitigating milestones toward submission of new drug applications and clinical trials.