The dual interaction with integrins and neuropilin‐1 receptor is the peculiar feature of iRGD peptide. Hence, in the present study, two iRGD peptide analogs were synthesized with DOTAGA and NODAGA as bifunctional chelator and aminohexanoic acid as a spacer for radiometalation with ⁶⁸GaCl₃. Negatively charged ⁶⁸Ga‐DOTAGA‐iRGD and neutral ⁶⁸Ga‐NODAGA‐iRGD radiotracers were investigated through in vitro cell uptake studies and in vivo biodistribution studies. Significant internalization of radiotracers in murine melanoma B16F10 cells was observed during in vitro studies. During in vivo studies, tumor uptake was higher for neutral ⁶⁸Ga‐NODAGA‐iRGD, but ⁶⁸Ga‐DOTAGA‐iRGD exhibited better tumor‐to‐blood ratio due to faster blood clearance. High kidney uptake of the two radiotracers was the limitation, which needs to be resolved through modification either in the peptide backbone or spacer/chelator.

中文翻译：

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68用DOTAGA和NODAGA螯合剂功能化的内在化RGD（iRGD）肽的Ga标记。

与整联蛋白和Neuropilin-1受体的双重相互作用是iRGD肽的独特特征。因此，在本研究中，合成了两种iRGD肽类似物，其中DOTAGA和NODAGA为双功能螯合剂，氨基己酸为间隔物，用于用⁶⁸ GaCl ₃进行放射性金属化。通过体外细胞摄取研究和体内生物分布研究对带负电的⁶⁸ Ga-DOTAGA-iRGD和中性⁶⁸ Ga-NODAGA-iRGD放射性示踪剂进行了研究。在体外研究中，观察到鼠黑色素瘤B16F10细胞中放射性示踪剂的明显内在化。在体内研究期间，中性⁶⁸ Ga-NODAGA-iRGD的肿瘤摄取更高，但⁶⁸由于血液清除速度更快，Ga‐DOTAGA‐iRGD表现出更好的肿瘤血比。局限性是两种放射性示踪剂的高肾脏摄取，这需要通过修饰肽主链或间隔子/螯合剂来解决。