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

Abstract

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 in vivo ([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 ex vivo 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 in vivo and ex vivo.