MELANOMA RADIOTHERAPY- PEPTIDE TARGETED ALPHA-RADIATION

描述(改编自应用程序)：拟议研究的目标 就是开发一种有效的放射治疗剂来治疗癌症 恶性黑素瘤。Re环化的α-黑素细胞刺激素 (Alpha-MSH)类似物ReCCMSH将用于靶向黑色素瘤肿瘤 发射放射性金属铋-212或其母同位素铅-212的阿尔法粒子。这个 ReCCMSH多肽与黑色素瘤表面的α-MSH受体具有高亲和力 细胞，并在结合时迅速内化。ReCCMSH将结合到 用铅-212标记的DOTA金属络合物。父辈 PB-212[(DOTA)-ReCCMSH]络合物将被用作体内Bi212[DOTA-ReCCMSH] 由于铋-212的半衰期较短，因此可能会产生较大的能量损失。铅-212-和 BI-212[DOTA-ReCCMSH]分子将接受放射化学检查 α-MSH受体的体外稳定性和亲和力 体内的生物分布和肿瘤靶向性。的发病率。 恶性黑色素瘤呈上升趋势。恶性黑色素瘤对 常规的化疗和外照射疗法。有选择地交付 一种高能、短程、发射阿尔法粒子的放射性金属 黑色素瘤细胞将产生致命剂量的肿瘤，同时减少侧枝循环 暴露重要器官和组织。 建议的商业应用：不可用

DESCRIPTION (Adapted from the application): The goal of the proposed research is to develop an efficacious radiotherapeutic agent for the treatment of malignant melanoma. A rhenium cyclized alpha-melanocyte stimulating hormone (alpha-MSH) analog ReCCMSH will be used to target melanoma tumors with the alpha particle emitting radiometal Bi-212, or its parent isotope Pb-212. The ReCCMSH peptide has a high affinity for alpha-MSH receptors present on melanoma cells and is rapidly internalized upon binding. ReCCMSH will be conjugated to the DOTA metal chelate and radiolabeled with Pb-212. The parent Pb-212[(DOTA)-ReCCMSH] complex will be used as an in vivo Bi-212[DOTA-ReCCMSH] generator, due to the short half-life of Bi-212. Both the Pb-212- and Bi-212[DOTA-ReCCMSH] molecules will be examined for their radiochemical stabilities and alpha-MSH receptor affinities in vitro and for their biodistribution and tumor targeting properties in vivo. The incidence of malignant melanoma is on the rise. Malignant melanoma is resistant to conventional chemo- and external beam radiation therapy. Selective delivery of a high-energy, short path length, alpha-particle-emitting radiometal to melanoma cells will yield a lethal dose to the tumor while reducing collateral exposures of vital organs and tissues. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE