Department of Radiology, University of Colorado Denver, Aurora, Colorado 80045, United States.
Department of Medical Oncology, University of Colorado Denver, Aurora, Colorado 80045, United States.
Bioconjug Chem. 2023 May 17;34(5):934-940. doi: 10.1021/acs.bioconjchem.3c00164. Epub 2023 May 4.
The purpose of this study was to evaluate the effect of linkers on tumor targeting and biodistribution of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH {[Tc]Tc(CO)-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-polyethylene glycol-Nle-c[Asp-His-d-Phe-Arg-Trp-Lys]-CONH} and [Tc]Tc(CO)-NOTA-AocNle-CycMSH {[Tc]Tc(CO)-NOTA-8-aminooctanoic acid-Nle-CycMSH} on B16/F10 melanoma-bearing mice. NOTA-PEGNle-CycMSH and NOTA-AocNle-CycMSH were synthesized and radiolabeled with [Tc]Tc via the {[Tc]Tc(CO)(OH)} intermediate. The biodistribution of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH and [Tc]Tc(CO)-NOTA-AocNle-CycMSH was determined on B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH was determined on B16/F10 melanoma-bearing C57 mice. [Tc]Tc(CO)-NOTA-PEGNle-CycMSH and [Tc]Tc(CO)-NOTA-AocNle-CycMSH were readily prepared with more than 90% radiochemical yields and exhibited MC1R-specific binding on B16/F10 melanoma cells. [Tc]Tc(CO)-NOTA-PEGNle-CycMSH exhibited a higher tumor uptake than [Tc]Tc(CO)-NOTA-AocNle-CycMSH at 2, 4, and 24 h postinjection. The tumor uptake of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH was 13.63 ± 1.13, 31.93 ± 2.57, 20.31 ± 3.23, and 1.33 ± 0.15% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. The tumor uptake of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH was 1.6 and 3.4 times the tumor uptake of [Tc]Tc(CO)-NOTA-AocNle-CycMSH at 2 and 4 h postinjection, respectively. Meanwhile, the normal organ uptake of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH was lower than 1.8% ID/g at 2 h postinjection. The renal uptake of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH was only 1.73 ± 0.37, 0.73 ± 0.14, and 0.03 ± 0.01% ID/g at 2, 4, and 24 h postinjection, respectively. [Tc]Tc(CO)-NOTA-PEGNle-CycMSH showed high tumor to normal organ uptake ratios at 2 h postinjection. Single-photon emission computed tomography imaging revealed that the B16/F10 melanoma lesions could be clearly visualized by [Tc]Tc(CO)-NOTA-PEGNle-CycMSH at 2 h postinjection. Overall, the high tumor uptake and low kidney uptake of [Tc]Tc(CO)-NOTA-PEGNle-CycMSH highlighted its potential for melanoma imaging and warranted the future evaluation of [Re]Re(CO)-NOTA-PEGNle-CycMSH for melanoma therapy.
本研究旨在评估连接子对 [Tc]Tc(CO)-NOTA-PEGNle-CycMSH {[Tc]Tc(CO)-1,4,7-三氮杂环壬烷-1,4,7-三基三乙酸-聚乙二醇-Nle-c[Asp-His-d-Phe-Arg-Trp-Lys]-CONH} 和 [Tc]Tc(CO)-NOTA-AocNle-CycMSH {[Tc]Tc(CO)-NOTA-8-氨基辛酸-Nle-CycMSH} 在 B16/F10 黑色素瘤荷瘤小鼠中的肿瘤靶向和生物分布的影响。NOTA-PEGNle-CycMSH 和 NOTA-AocNle-CycMSH 通过 {[Tc]Tc(CO)(OH)} 中间体与 [Tc]Tc 标记合成。在 B16/F10 黑色素瘤荷瘤 C57 小鼠中测定了 [Tc]Tc(CO)-NOTA-PEGNle-CycMSH 和 [Tc]Tc(CO)-NOTA-AocNle-CycMSH 的生物分布。在 B16/F10 黑色素瘤荷瘤 C57 小鼠中测定了 [Tc]Tc(CO)-NOTA-PEGNle-CycMSH 的黑色素瘤成像特性。[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 和 [Tc]Tc(CO)-NOTA-AocNle-CycMSH 易于制备，放射化学产率超过 90%，并在 B16/F10 黑色素瘤细胞上表现出 MC1R 特异性结合。[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 在注射后 2、4 和 24 小时的肿瘤摄取量高于 [Tc]Tc(CO)-NOTA-AocNle-CycMSH。[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 的肿瘤摄取率分别为 0.5、2、4 和 24 小时后 13.63 ± 1.13、31.93 ± 2.57、20.31 ± 3.23 和 1.33 ± 0.15% ID/g。[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 的肿瘤摄取率分别是 [Tc]Tc(CO)-NOTA-AocNle-CycMSH 在 2 和 4 小时的肿瘤摄取率的 1.6 和 3.4 倍。同时，[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 在注射后 2 小时的正常器官摄取量低于 1.8% ID/g。[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 的肾脏摄取量分别为 2、4 和 24 小时后 1.73 ± 0.37、0.73 ± 0.14 和 0.03 ± 0.01% ID/g。[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 在注射后 2 小时显示出较高的肿瘤与正常器官摄取比。单光子发射计算机断层扫描成像显示，[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 在注射后 2 小时可清晰显示 B16/F10 黑色素瘤病灶。总的来说，[Tc]Tc(CO)-NOTA-PEGNle-CycMSH 的高肿瘤摄取和低肾脏摄取突出了其用于黑色素瘤成像的潜力，值得进一步评估 [Re]Re(CO)-NOTA-PEGNle-CycMSH 用于黑色素瘤治疗。
