本研究的目的是研究布洛芬 (IBU) 的引入如何影响 177Lu 标记的 IBU 结合的 α-黑素细胞刺激激素肽的肿瘤靶向和生物分布特性。 IBU 用作白蛋白结合剂，并与不带或带接头的 DOTA-Lys 部分缀合，产生 DOTA-Lys(IBU)-GG-Nle-CycMSHhex {1,4,7,10-四氮杂环十二烷-1,4， 7,10-四乙酸-Lys(IBU)-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}，DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex，DOTA -Lys(Asn-IBU)-GGNle-CycMSHhex 和 DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex 肽。首先在 B16/F10 黑色素瘤细胞上测定了它们的黑皮质素受体 1 (MC1R) 结合亲和力。然后在注射后2小时测定177Lu标记肽在携带黑色素瘤的B16/F10 C57小鼠上的生物分布，以选择先导肽进行进一步检查。使用携带黑色素瘤的 B16/F10 C57 小鼠进一步评估了 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex 的完整生物分布和黑色素瘤成像特性。 DOTA-Lys(IBU)-GG-Nle-CycMSHhex、DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex、DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex 和 DOTA-Lys(Dab-IBU)-GGNle -CycMSHhex 对 B16/F10 黑色素瘤细胞的 IC50 值分别为 1.41 ± 0.37、1.52 ± 0.08、0.03 ± 0.01 和 0.58 ± 0.06 nM。 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex 在所有四种设计的 177Lu 肽中表现出最低的肝脏和肾脏摄取量。因此，进一步评估了 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex 的完整生物分布和黑色素瘤成像特性。 B16/F10 黑色素瘤对 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex 的摄取在 0.5、2、4 和 4 时分别为 19.5 ± 3.12、24.12 ± 3.35、23.85 ± 2.08 和 10.80 ± 2.89% ID/g。分别为注射后24小时。此外，177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex 可以在注射后 2 小时清晰地显示 B16/F10 黑色素瘤病变。带或不带接头的 IBU 与 GGNle-CycMSHhex 的缀合会影响设计肽的 MC1R 结合亲和力。连接子的电荷在肝脏和肾脏摄取 177Lu-Asp-IBU、177Lu-Asn-IBU 和 177Lu-Dab-IBU 中发挥关键作用。 177Lu-Asp-IBU 表现出比 177Lu-Asn-IBU 和 177Lu-Dab-IBU 更高的肿瘤/肝脏和肿瘤/肾脏摄取比，强调了其在未来黑色素瘤治疗中的潜在评估。

The purpose of this study was to examine how the introduction of ibuprofen (IBU) affected tumor-targeting and biodistribution properties of 177Lu-labeled IBU-conjugated alpha-melanocyte-stimulating hormone peptides. The IBU was used as an albumin binder and conjugated to the DOTA-Lys moiety without or with a linker to yield DOTA-Lys(IBU)-GG-Nle-CycMSHhex {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Lys(IBU)-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex peptides. Their melanocortin-receptor 1 (MC1R) binding affinities were determined on B16/F10 melanoma cells first. Then the biodistribution of 177Lu-labeled peptides was determined on B16/F10 melanoma-bearing C57 mice at 2 h postinjection to choose the lead peptide for further examination. The full biodistribution and melanoma imaging properties of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex were further evaluated using B16/F10 melanoma-bearing C57 mice. DOTA-Lys(IBU)-GG-Nle-CycMSHhex, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex displayed the IC50 values of 1.41 ± 0.37, 1.52 ± 0.08, 0.03 ± 0.01, and 0.58 ± 0.06 nM on B16/F10 melanoma cells, respectively. 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex exhibited the lowest liver and kidney uptake among all four designed 177Lu peptides. Therefore, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was further evaluated for its full biodistribution and melanoma imaging properties. The B16/F10 melanoma uptake of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was 19.5 ± 3.12, 24.12 ± 3.35, 23.85 ± 2.08, and 10.80 ± 2.89% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Moreover, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex could clearly visualize the B16/F10 melanoma lesions at 2 h postinjection. The conjugation of IBU with or without a linker to GGNle-CycMSHhex affected the MC1R binding affinities of the designed peptides. The charge of the linker played a key role in the liver and kidney uptake of 177Lu-Asp-IBU, 177Lu-Asn-IBU, and 177Lu-Dab-IBU. 177Lu-Asp-IBU exhibited higher tumor/liver and tumor/kidney uptake ratios than those of 177Lu-Asn-IBU and 177Lu-Dab-IBU, underscoring its potential evaluation for melanoma therapy in the future.