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

转移性黑色素瘤几乎都是致命的，因为对所有治疗都产生了抵抗力。而当 最近FDA批准的药物正在获得轰动一时的地位(例如，Zelboraf)，预期寿命增加了 仅仅几个月，副作用很严重。虽然放射性核素疗法的商业潜力得到了证明 通过最近的介绍(例如，Xofigo)，该方法尚未被引入到转移性黑色素瘤。在这 建议，我们确定一种新的联合图像引导的放射性核素治疗转移的可行性。 使用我们新的[203/212Pb]标记产品(DOTA-VMT-MCR1和DOTA-RMX-GC)治疗黑色素瘤 具有高亲和力和特异性的黑色素瘤特异性分子靶点。在拟议的研究中，我们将 确定DOTA-VMT-MCR1/DOTA-RMX-GC作为独立配体和多受体的商业可行性。 同时靶向MCR1/GLUT的靶向杂交体，用于图像引导的放射性核素治疗。这个 第一阶段SBIR的目标是：(1)确定放射合成[~(212)Pb]DOTA-RMX-GC的可行性 和[212Pb]DOTA-VMT-MCR1；(2)评估[212Pb]DOTARMX的可行性。 GC和[212Pb]DOTA-VMT-MCR1治疗黑色素瘤荷瘤小鼠；以及(3)测定 双靶向(GLUT1/MCR1)生物结合物用于放射性核素显像和治疗转移瘤的可行性 黑色素瘤。随着这些目标的实现，我们希望通过降低风险来推进我们的化合物 提交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.