PET & Cyclotron Centre, Department of Nuclear Medicine, Odense University Hospital, 5000 Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.
Molecules. 2020 Dec 18;25(24):5993. doi: 10.3390/molecules25245993.
Gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of prostate cancers. This study aimed to investigate the potential of Cu (radionuclide for late time-point PET-imaging) for imaging of GRPR expression using NOTA-PEG-RM26 and NODAGA-PEG-RM26. Methods: NOTA/NODAGA-PEG-RM26 were labeled with Cu and evaluated in GRPR-expressing PC-3 cells. Biodistribution of [Cu]Cu-NOTA/NODAGA-PEG-RM26 was studied in PC-3 xenografted mice and compared to the biodistribution of [Co]Co-NOTA/NODAGA-PEG-RM26 at 3 and 24 h p.i. Preclinical PET/CT imaging was performed in tumor-bearing mice. NOTA/NODAGA-PEG-RM26 were stably labeled with Cu with quantitative yields. In vitro, binding of [Cu]Cu-NOTA/NODAGA-PEG-RM26 was rapid and GRPR-specific with slow internalization. In vivo, [Cu]Cu-NOTA/NODAGA-PEG-RM26 bound specifically to GRPR-expressing tumors with fast clearance from blood and normal organs and displayed generally comparable biodistribution profiles to [Co]Co-NOTA/NODAGA-PEG-RM26; tumor uptake exceeded normal tissue uptake 3 h p.i.. Tumor-to-organ ratios did not increase significantly with time. [Cu]Cu-NOTA-PEG-RM26 had a significantly higher liver and pancreas uptake compared to other agents. Co-labeled radioconjugates showed overall higher tumor-to-non-tumor ratios, compared to the Cu-labeled counterparts. [Cu]Cu-NOTA/NODAGA-PEG-RM26 was able to visualize GRPR-expression in a murine PC model using PET. However, [Co]Co-NOTA/NODAGA-PEG-RM26 provided better in vivo stability and overall higher tumor-to-non-tumor ratios compared with the Cu-labeled conjugates.
胃泌素释放肽受体 (GRPR) 在大多数前列腺癌中过度表达。本研究旨在使用 NOTA-PEG-RM26 和 NODAGA-PEG-RM26 研究 Cu（用于后期 PET 成像的放射性核素）用于 GRPR 表达成像的潜力。
用 Cu 标记 NOTA/NODAGA-PEG-RM26 ，并在表达 GRPR 的 PC-3 细胞中进行评估。在 PC-3 异种移植小鼠中研究 [Cu]Cu-NOTA/NODAGA-PEG-RM26 的生物分布，并与 3 和 24 h p.i. 的 [Co]Co-NOTA/NODAGA-PEG-RM26 的生物分布进行比较。在荷瘤小鼠中进行临床前 PET/CT 成像。NOTA/NODAGA-PEG-RM26 被 Cu 定量标记。体外，[Cu]Cu-NOTA/NODAGA-PEG-RM26 的结合快速且具有 GRPR 特异性，随后缓慢内化。在体内，[Cu]Cu-NOTA/NODAGA-PEG-RM26 特异性结合表达 GRPR 的肿瘤，从血液和正常器官中快速清除，并显示与 [Co]Co-NOTA/NODAGA-PEG-RM26 相当的生物分布谱；3 h p.i.时肿瘤摄取超过正常组织摄取。随着时间的推移，肿瘤与器官的比值没有显著增加。与其他试剂相比，[Cu]Cu-NOTA-PEG-RM26 对肝脏和胰腺的摄取明显更高。与 Cu 标记的对应物相比，共标记的放射性缀合物总体上具有更高的肿瘤与非肿瘤比值。[Cu]Cu-NOTA/NODAGA-PEG-RM26 能够使用 PET 可视化小鼠 PC 模型中的 GRPR 表达。然而，与 Cu 标记的缀合物相比，[Co]Co-NOTA/NODAGA-PEG-RM26 提供了更好的体内稳定性和总体更高的肿瘤与非肿瘤比值。
