Although ¹⁸F-5-fluoro-N-(2-[diethylamino]ethyl)picolinamide (¹⁸F-5-FPN) is considered a promising radiopharmaceutical for PET imaging of melanoma, it accumulates at high concentrations in the liver. The aim in this research was to optimize the structure of ¹⁸F-5-FPN with triethylene glycol to reduce liver uptake as well as improve pharmacokinetics, and to evaluate its performance in detection of melanoma liver and lung metastases. ¹⁸F-PEG₃-FPN was successfully prepared with a high radiolabeling yield (44.68% ± 5.99%) and radiochemical purity (>99%). The uptake of ¹⁸F-PEG₃-FPN by pigmented B16F10 melanoma cells was significantly higher than that by amelanotic melanoma A375 cells. The binding to B16F10 cells could be blocked by excess ¹⁹F-PEG₃-FPN. On small animal PET images, B16F10 tumors, but not A375 tumors, were clearly delineated after ¹⁸F-PEG₃-FPN injection. More importantly, ¹⁸F-PEG₃-FPN uptake by liver (2.27 ± 0.45 and 1.74 ± 0.35% ID/g, at 1 and 2 h) was significantly lower than that of ¹⁸F-5-FPN, and the lesions in lung and liver could be clearly detected by ¹⁸F-PEG₃-FPN PET imaging in mouse models of pulmonary or hepatic metastases. Overall, we successfully synthesized ¹⁸F-PEG₃-FPN, which has higher labeling efficacy and better in vivo pharmacokinetics along with lower liver uptake compared to ¹⁸F-5-FPN. This suggests ¹⁸F-PEG₃-FPN as a candidate for pigmented melanoma liver and lung metastasis detection.

中文翻译：

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¹⁸ F-PEG ₃ -FPN的合成及临床前评价对转移性黑色素瘤的检测

尽管¹⁸ F-5-氟-N-（2- [二乙基氨基]乙基）吡啶啉酰胺（¹⁸ F-5-FPN）被认为是用于PET成像黑色素瘤的有前途的放射性药物，但它在肝脏中以高浓度积累。这项研究的目的是用三甘醇优化¹⁸ F-5-FPN的结构，以减少肝脏摄取并改善药代动力学，并评估其在检测黑色素瘤肝和肺转移中的性能。成功制备了¹⁸ F-PEG ₃ -FPN，具有较高的放射标记产率（44.68％±5.99％）和放射化学纯度（> 99％）。摄取¹⁸ F-PEG ₃着色的B16F10黑色素瘤细胞的-FPN显着高于黑色素瘤黑色素瘤A375细胞的-FPN。与B16F10细胞的结合可能被过量的¹⁹ F-PEG ₃ -FPN阻断。在小动物PET图像上，在注射¹⁸ F-PEG ₃ -FPN后清楚地描绘出B16F10肿瘤，而不是A375肿瘤。更重要的是，肝脏对¹⁸ F-PEG ₃ -FPN的摄取（在1和2 h时为2.27±0.45和1.74±0.35％ID / g）显着低于¹⁸ F-5-FPN，并且肺部病变¹⁸ F-PEG ₃可以清楚地检测到肝脏-FPN PET成像在肺或肝转移的小鼠模型中。总的来说，我们成功地合成了¹⁸ F-PEG ₃ -FPN，与¹⁸ F-5-FPN相比，它具有更高的标记功效和更好的体内药代动力学以及更低的肝脏摄取。这表明¹⁸ F-PEG ₃ -FPN作为色素性黑色素瘤肝和肺转移检测的候选者。