在临床前和临床研究中，NeoB和RM2是最常研究的胃泌素释放肽受体（GRPR）靶向放射追踪剂。因此，对这两种放射追踪剂进行广泛的并置比较，以确定是否有一种优于另一种的优势，具有重要的价值。因此，本研究旨在比较放射标记的NeoB和RM2的体外和体内特性，以指导未来的临床研究。对放射标记的GRPR模拟物在磷酸盐缓冲生理盐水（PBS）和市售的小鼠和人类血清中的稳定性进行了测定。通过将人前列腺癌PC-3细胞与[177Lu]Lu-NeoB或[177Lu]Lu-RM2一起孵育，+ / -逐渐增加未标记的NeoB，RM2或Tyr4-炸弹素（BBN），确定目标亲和力。为了确定摄取和特异性，将细胞与[177Lu]Lu-NeoB或[177Lu]Lu-RM2一起孵育，+ / -Tyr4-BBN。此外，还进行了体内研究以确定生物分布和药代动力学。最后，对各种表达GRPR的人类癌组织进行了放射追踪剂结合研究。这两种放射追踪剂在PBS和人血清中都表现出很高的稳定性，但在小鼠血清中的稳定性随着时间的推移而显著降低。此外，这两种放射追踪剂都表现出很高的GRPR亲和力和特异性，但在体外研究中观察到了[177Lu] Lu-NeoB的更高摄取量。在体内，未观察到肿瘤摄取的差异。在生理器官中，摄取的主要差异观察到了GRPR表达的胰腺中; [177Lu]Lu-RM2的胰腺摄取较低，并且胰腺半衰期较短，而[177Lu]Lu-NeoB的胰腺摄取较高。此外，[177Lu]Lu-RM2的瘤体对肾脏的比值较低，而[177Lu]Lu-NeoB的瘤体对血液的比值较低。放射自显影研究显示，放射标记的NeoB与所有人类肿瘤组织的结合较高。基于这些发现，我们得出结论，放射标记的NeoB和RM2的体内肿瘤靶向能力相似。有关这些放射追踪剂应用于治疗目的时，所观察到的生理器官摄取（例如胰腺，肾脏和血液）是否导致有关器官吸收剂量的显著差异，还需要进一步研究来确定。© 2023. 作者（们）。

NeoB and RM2 are the most investigated gastrin-releasing peptide receptor (GRPR)-targeting radiotracers in preclinical and clinical studies. Therefore, an extensive side-by-side comparison of the two radiotracers is valuable to demonstrate whether one has advantages over the other. Accordingly, this study aims to compare the in vitro and in vivo characteristics of radiolabeled NeoB and RM2 to guide future clinical studies.The stability of the radiolabeled GRPR analogs was determined in phosphate buffered saline (PBS), and commercially available mouse and human serum. Target affinity was determined by incubating human prostate cancer PC-3 cells with [177Lu]Lu-NeoB or [177Lu]Lu-RM2, + / - increasing concentrations of unlabeled NeoB, RM2, or Tyr4-bombesin (BBN). To determine uptake and specificity cells were incubated with [177Lu]Lu-NeoB or [177Lu]Lu-RM2 + / - Tyr4-BBN. Moreover, in vivo studies were performed to determine biodistribution and pharmacokinetics. Finally, radiotracer binding to various GRPR-expressing human cancer tissues was investigated.Both radiotracers demonstrated high stability in PBS and human serum, but stability in mouse serum decreased substantially over time. Moreover, both radiotracers demonstrated high GRPR affinity and specificity, but a higher uptake of [177Lu]Lu-NeoB was observed in in vitro studies. In vivo, no difference in tumor uptake was seen. The most prominent difference in uptake in physiological organs was observed in the GRPR-expressing pancreas; [177Lu]Lu-RM2 had less pancreatic uptake and a shorter pancreatic half-life than [177Lu]Lu-NeoB. Furthermore, [177Lu]Lu-RM2 presented with a lower tumor-to-kidney ratio, while the tumor-to-blood ratio was lower for [177Lu]Lu-NeoB. The autoradiography studies revealed higher binding of radiolabeled NeoB to all human tumor tissues.Based on these findings, we conclude that the in vivo tumor-targeting capability of radiolabeled NeoB and RM2 is similar. Additional studies are needed to determine whether the differences observed in physiological organ uptakes, i.e., the pancreas, kidneys, and blood, result in relevant differences in organ absorbed doses when the radiotracers are applied for therapeutic purposes.© 2023. The Author(s).