Abstract
Develop a 64Cu labeled radiopharmaceutical targeting prostate specific membrane antigen (PSMA) and investigate its application for prostate cancer imaging. 64Cu-PSMA-BCH was prepared and investigated for stability, PSMA specificity, and micro-PET imaging. With the approval of Ethics Committee of Beijing Cancer Hospital (No. 2017KT97), PET/CT imaging in 4 patients with suspected prostate cancer was performed and the radiation dosimetry was estimated. Then, PSMA PET-ultrasound image-guided biopsies were performed on 3 patients and the fine needle aspirates were further performed for autoradiography and immunohistochemistry analysis. 64Cu-PSMA-BCH was prepared with high radiochemical yield and stability. In vivo study showed higher uptake in PSMA ( +) 22Rv1 cells than PSMA ( -) PC-3 cells (5.59 ± 0.36 and 1.97 ± 0.22 IA%/106 cells at 1h). It accumulated in 22Rv1 tumor with increasing radioactivity uptake and T/N ratios from 1 to 24h post-injection. In patients with suspected prostate cancer, SUVmax and T/N ratios increased within 24h post-injection. Compared with image at 1h post-injection, more tumor lesions were detected at 6h and 24h post-injection. The human organ radiation dosimetry showed gallbladder wall was most critical, liver and kidneys were followed, and the whole-body effective dose was 0.0292mSv/MBq. Two fine needle aspirates obtained by PET-ultrasound-guided targeted biopsy showed high radioactive signal by autoradiography, with 100% PSMA expression in cytoplasm and 30% expression in nucleus. 64Cu-PSMA-BCH was PSMA specific and showed high stability in vivo with lower uptake in liver than 64Cu-PSMA-617. Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry. The increased tumor uptake and T/N ratios by delayed imaging may facilitate the detection of small lesions and guiding targeted biopsies.
Highlights
Prostate cancer (PCa) is common among men
64Cu-prostate specific membrane antigen (PSMA)-BCH was prepared with high radiochemical yield and stability
Biodistribution in mice and PCa patients showed similar profile compared with other PSMA ligands and it was safe with moderate effective dosimetry
Summary
Prostate cancer (PCa) is common among men. PSMA PET/CT has shown high sensitivity and specificity in identifying sites of PCa, and some studies have demonstrated that PSMA-based PET/CT and PET/MR can give accurate location of tumor lesions in primary PCa superior to MRI [1, 2], which offers the possibility that PSMA PET images prior to biopsy giving a simpler criteria for targeted biopsy. Limited by the short half-life of 68Ga, the images were obtained at 1 h post injection (p.i.) with high radioactivity in bladder, which lead the low contrast between the PCa and background. Radiopharmaceuticals labeled with radionuclides having longer half-life can be used in delayed imaging, potentially leading to higher tumor-to-background contrast. Because of the internalization of PSMA radiotracers, the contrast in tumor lesions increases at longer time points after injection, with the radioactivity in non-target organs significantly decreasing at later time points. Among such radionuclides, copper-64 (64Cu) was deemed to be a good choice due to its moderate half-life (12.7 h) and high resolution [4]
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