Comparison of the Effects of DOTA and NOTA Chelators on 64Cu-Cudotadipep and 64Cu-Cunotadipep for Prostate Cancer

Background: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic (NOTA) as 64Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, 64Cu-cudotadipep 64Cu-cunotadipep, on pharmacokinetics. Methods: The vitro stability chelators was evaluated using human mouse serum. In PSMA-binding affinity cell uptake were 22Rv1 cells. To evaluate specific PSMA-expressing tumor-targeting efficiency, micro-positron emission tomography (mcroPET)/computed (CT) biodistribution analysis performed PSMA+ PC3-PIP PSMA− PC3-flu tumor xenografts. Results: serum DOTA- or NOTA-conjugated 64Cu-cunotadipep >97%. Ki value NOTA derivative, cunotadipep, binding higher (2.17 ± 0.25 nM) than that DOTA cudotadipep (6.75 0.42 nM). cunotadipep exhibited a cellular (6.02 0.05%/1 × 106 cells) with (2.93 0.06%/1 cells). microPET/CT imaging, 64Cu-labeled demonstrated greater lower liver derivative. Conclusions: indicates PSMA-targeted can be applied clinical practice owing to its high diagnostic power for prostate cancer.