<i>In vivo</i> Evaluation of Copper-61-Labeled Prostate-specific Membrane Antigen Targeting Novel Radiopharmaceutical: First Steps toward Clinical Implementation

The introduction of radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) has revolutionized the molecular imaging of prostate cancer (PCa); however, due to the potential downsides of the commonly used labeling entities (gallium-68/fluorine-18), the role of alternative isotopes is emerging. Given the desirable physical characteristics of positron emitter copper-61 (⁶¹Cu), herein, a novel PSMA PET probe using the recently introduced KFTG chelator was developed and tested <i>in vivo</i> ([⁶¹Cu]-Cu-KFTG-PSMA). Pharmacokinetics was assessed in PSMA⁺ LNCaP PCa xenografts and healthy counterparts using micro-PET imaging, biodistribution, and competition studies. The uptake of [⁶¹Cu]-Cu-KFTG-PSMA in LNCaP tumor lesions showed a trend to increase from 30 to 180 min post-injection (SUVmean: 1.50 ± 0.19-2.18 ± 0.25). In comparison, healthy organs demonstrated low radioactivity and fast body clearance, yielding better contrast for later time point images. Likewise, gradually increasing tumor retention was observed <i>ex vivo</i> as well (11.4 ± 1.4, 12.6 ± 1.6, and 13.8 ± 2.1%ID/g at 30, 90, and 180 min post-injection, respectively); however, some gastrointestinal organs presented moderate early time point accumulation. Followed by pretreatment with cold PSMA, blocked LNCaP tumors showed hardly any radioactivity, which further confirmed high target specificity both <i>in vivo</i> and <i>ex vivo</i>.