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

The purpose of this study was to investigate the most appropriate methodological approach for the automatic measurement of rodent myocardial infarct polar map using histogram-based thresholding and unsupervised deep learning (DL)-based segmentation. A rat myocardial infarction model was induced by ligation of the left coronary artery. Positron emission tomography (PET) was performed 60 min after the administration of ¹⁸F-fluoro-deoxy-glucose (¹⁸F-FDG), and PET was performed after injecting ⁶⁴Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone). Single photon emission computed tomography was performed 60 min after injection of ^99mTc-hexakis-2-methoxyisobutylisonitrile and ²⁰¹Tl. Delayed contrast-enhanced magnetic resonance imaging was performed after injecting Gd-DTPA-BMA. Three types of thresholding methods (naive thresholding, Otsu’s algorithm, and multi-Gaussian mixture model (MGMM)) were used. DL segmentation methods were based on a convolution neural network and trained with constraints on feature similarity and spatial continuity of the response map extracted from images by the network. The relative infarct sizes measured by histology and estimated R² for ¹⁸F-FDG were 0.8477, 0.7084, 0.8353, and 0.9024 for naïve thresholding, Otsu’s algorithm, MGMM, and DL segmentation, respectively. DL-based method improved the accuracy of MI size assessment.