MELANOMA RADIOTHERAPY- PEPTIDE TARGETED ALPHA-RADIATION

描述（改编自申请）：拟议研究的目标 是开发一种有效的放射治疗剂， 恶性黑素瘤一种双环化α-黑素细胞刺激激素 （α-MSH）类似物ReCCMSH将用于靶向黑色素瘤肿瘤， 发射放射性金属Bi-212或其母体同位素Pb-212的α粒子。的 ReCCMSH肽对黑色素瘤上存在的α-MSH受体具有高亲和力 细胞，并在结合后迅速内化。ReCCMSH将与 DOTA金属螯合物并用Pb-212放射性标记。母 Pb-212[（DOTA）-ReCCMSH]络合物将用作体内Bi-212[DOTA-ReCCMSH] 由于Bi-212的半衰期较短，Pb-212和 将检查Bi-212[DOTA-ReCCMSH]分子的放射化学 体外稳定性和α-MSH受体亲和力以及它们的 体内生物分布和肿瘤靶向特性。的发生率 恶性黑色素瘤正在上升。恶性黑色素瘤对 常规化疗和体外放射治疗。选择性递送 一种高能量，短路径长度，α粒子发射的放射性金属， 黑色素瘤细胞将对肿瘤产生致命剂量，同时减少 重要器官和组织的暴露。 拟议商业应用：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