Targeted radionuclide therapy (TRT) targeting oncoproteins facilitates the delivery of therapeutic radionuclides to tumor tissues with high precision. Herein, we developed 2 new radiopharmaceuticals, 4-¹³¹I-iodo- and 4-²¹¹At-astato-N-[4-(6-(isopropylamino)pyridine-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide (¹³¹I-IITM and ²¹¹At-AITM), targeting the ectopic metabotropic glutamate receptor 1 (mGluR1) in melanomas for TRT studies. Methods: ¹³¹I-IITM and ²¹¹At-AITM were synthesized by reacting a stannyl precursor with ¹³¹I-NaI and ²¹¹At in the presence of an oxidizing agent. The therapeutic efficacy and safety of the 2 radiopharmaceuticals were investigated using mGluR1-expressing B16F10 melanoma cells and melanoma-bearing mice. Results: ¹³¹I-IITM and ²¹¹At-AITM were obtained with a radiochemical purity of greater than 99% and radiochemical yields of 42.7% ± 10.4% and 45.7% ± 6.5%, respectively, based on the total radioactivity of used radionuclides. ¹³¹I-IITM and ²¹¹At-AITM exhibited a maximum uptake of 4.66% ± 0.70 and 7.68% ± 0.71 percentage injected dose per gram (%ID/g) in the targeted melanomas, respectively, and were rapidly cleared from nontarget organs after intravenous injection. Both agents markedly inhibited melanoma growth compared with the controls (61.00% and 95.68%, respectively). In the melanoma model, considerably greater therapeutic efficacy with negligible toxicity was observed using ²¹¹At-AITM. Conclusion: The nontoxic radiopharmaceuticals ¹³¹I-IITM and ²¹¹At-AITM are useful high-precision TRT agents that can be used to target the oncoprotein mGluR1 for melanoma therapy.

靶向癌蛋白的靶向放射性核素治疗（TRT）有助于将治疗性放射性核素高精度地递送至肿瘤组织。在本文中，我们开发了2个新的放射性药物，4- ¹³¹ I-碘和4- ²¹¹ AT-astato- ñ - [4-（6-（异丙基氨基）吡啶-4-基）-1,3-噻唑-2-基] -N-甲基苯甲酰胺（¹³¹ I-IITM和²¹¹ At-AITM），针对TRT研究中黑色素瘤中的异位代谢型谷氨酸受体1（mGluR1）。方法： 使苯乙烯前体与¹³¹ I-NaI和²¹¹反应，合成¹³¹ I-IITM和²¹¹ At-AITM。在氧化剂的存在下。使用表达mGluR1的B16F10黑色素瘤细胞和带有黑色素瘤的小鼠研究了这两种放射性药物的疗效和安全性。结果： 基于所用放射性核素的总放射性，获得了¹³¹ I-IITM和²¹¹ At-AITM，其放射化学纯度大于99％，放射化学产率分别为42.7％±10.4％和45.7％±6.5％。¹³¹ I-IITM和²¹¹在目标黑色素瘤中，At-AITM的最大摄取量分别为每克（％ID / g）4.66％±0.70和7.68％±0.71百分比注射剂量，并且在静脉注射后迅速从非目标器官清除。与对照相比，两种药物均显着抑制黑色素瘤的生长（分别为61.00％和95.68％）。在黑素瘤模型中，使用²¹¹ At-AITM观察到明显更高的治疗效果，且毒性可忽略不计。结论：无毒放射性药物¹³¹ I-IITM和²¹¹ At-AITM是有用的高精度TRT试剂，可用于靶向癌蛋白mGluR1进行黑色素瘤治疗。