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Gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of prostate cancers. This study aimed to investigate the potential of 64 Cu (radionuclide for late time-point PET-imaging) for imaging of GRPR expression using NOTA-PEG 2 -RM26 and NODAGA-PEG 2 -RM26. Methods: NOTA/NODAGA-PEG 2 -RM26 were labeled with 64 Cu and evaluated in GRPR-expressing PC-3 cells. Biodistribution of [ 64 Cu]Cu-NOTA/NODAGA-PEG 2 -RM26 was studied in PC-3 xenografted mice and compared to the biodistribution of [ 57 Co]Co-NOTA/NODAGA-PEG 2 -RM26 at 3 and 24 h p.i. Preclinical PET/CT imaging was performed in tumor-bearing mice. NOTA/NODAGA-PEG 2 -RM26 were stably labeled with 64 Cu with quantitative yields. In vitro, binding of [ 64 Cu]Cu-NOTA/NODAGA-PEG 2 -RM26 was rapid and GRPR-specific with slow internalization. In vivo, [ 64 Cu]Cu-NOTA/NODAGA-PEG 2 -RM26 bound specifically to GRPR-expressing tumors with fast clearance from blood and normal organs and displayed generally comparable biodistribution profiles to [ 57 Co]Co-NOTA/NODAGA-PEG 2 -RM26; tumor uptake exceeded normal tissue uptake 3 h p.i.. Tumor-to-organ ratios did not increase significantly with time. [ 64 Cu]Cu-NOTA-PEG 2 -RM26 had a significantly higher liver and pancreas uptake compared to other agents. 57 Co-labeled radioconjugates showed overall higher tumor-to-non-tumor ratios, compared to the 64 Cu-labeled counterparts. [ 64 Cu]Cu-NOTA/NODAGA-PEG 2 -RM26 was able to visualize GRPR-expression in a murine PC model using PET. However, [ 55/57 Co]Co-NOTA/NODAGA-PEG 2 -RM26 provided better in vivo stability and overall higher tumor-to-non-tumor ratios compared with the 64 Cu-labeled conjugates.

molecules/molecules online/molecules annual

Preclinical Evaluation of the Copper-64 Labeled GRPR-Antagonist RM26 in Comparison with the Cobalt-55 Labeled Counterpart for PET-Imaging of Prostate Cancer