MIBG AND ANALOGS FOR DIAGNOSIS AND THERAPY

间碘苯甲基胍(MIBG)，具有多种结构组合 布雷利石和愈创木酚的特征。MIBG已被发现是一种 潜在的肾上腺髓质剂以及治疗 其他诊断和治疗应用。例如，MIBG， 放射性标记的碘-131和碘-123已用于 心脏异常和神经内分泌肿瘤的诊断。[131I]MIBG 也被用于治疗神经内分泌肿瘤。与 目前使用的方法(同位素交换)，放射性碘MIBG不能 在不添加载波的情况下获得(n.c.a.)水平。这可能会削弱其 某些应用的临床实用价值。在这方面有一些缺点 [131I]MIBG疗法，尤其是神经母细胞瘤，归因于 碘-131的物理特性。的物理特征 司他丁-211更适用于神经母细胞瘤的治疗 因为Astatine-211释放出高线性能量转移的阿尔法粒子。 用正电子标记MIBG类似物可能是有利的- 发射用于正电子发射断层成像的核素。这个 这项建议的目标是开发合成方法，用于 北卡罗来纳州的制备。[131I]MIBG，3- [211At][211At][211At]3- [18F]氟苄基胍([18F]MFBG)和4-[18F]氟-3- [18F][FIBG]及其潜在的应用价值 诊断和治疗性放射性药物。首先，试管内 每一种新试剂的结合特性都将使用 神经母细胞瘤细胞系。这些药物的生物分布将是 最初在正常小鼠中测定，随后在无瘤小鼠中测定 人神经母细胞瘤异种移植模型。这些研究应该给出 关于这些药物作为MIBG类似物的潜在用途的信息。

Meta-iodobenzylguanidine (MIBG), has a combination of the structural features of bretyllium and guanethedine. MIBG has been found to be a potential adrenomedullary agent as well as a radiopharmaceutical for other diagnostic and therapeutic applications. For example, MIBG, radiolabeled with iodine-131 and iodine-123, has been used in the diagnosis of heart abnormalities and neuroendocrine tumors. [131I]MIBG also has been used for the treatment of neuroendocrine tumors. With the currently used method (isotopic exchange), radioiodinated MIBG cannot be obtained at a no-carrier-added (n.c.a.) level. This may diminish its clinical utility for some applications. there are some shortcomings in [131I]MIBG therapy, especially for neuroblastoma, attributed to the physical characteristics of iodine-131. The physical characteristics of astatine-211 could be more suitable for the treatment of neuroblastoma since astatine-211 emits alpha particles of high linear energy transfer. It may be advantageous to have MIBG analogs labeled with positron- emitting nuclides for positron emission tomographic imaging. The objectives of this proposal are to develop synthetic methods for the preparation of n.c.a. [131I]MIBG,3- [211At]astatobenzylguanidine([211At]MABG)3- [18F]fluorobenzylguanidine([18F]MFBG) and 4-[18F]fluoro-3- iodobenzylguanidine([18F]FIBG) and to evaluate their potential as diagnostic and therapeutic radiopharmaceuticals. First, the in vitro binding characteristics of each of the new agents will be studied using neuroblastoma cell lines. Biodistribution of these agents will be determined initially in normal mice and subsequently in athymic mouse human neuroblastoma xenograft models. These studies should give information on the potential utility of these agents as MIBG analogs.