A Bivalent Inhibitor of Prostate Specific Membrane Antigen Radiolabeled with Copper‐64 with High Tumor Uptake and Retention

Abstract

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Image-Guided Surgery: Are We Getting the Most Out of Small-Molecule Prostate-Specific-Membrane-Antigen-Targeted Tracers?

“…Cu-based derivatives (t 1/2 = 12.7 h, E max β + = 653 keV) 87 could potentially help to further extend the time interval between tracer administration and surgery.…”

Therapeutic Efficacy of a Bivalent Inhibitor of Prostate-Specific Membrane Antigen Labeled with 67Cu

“…64 Cu-CuSarbisPSMA has excellent uptake in LNCaP tumors in male NSG mice and importantly showed excellent retention in the tumor up to 24 h post injection (17), suggesting that the copper-67 variant may be suited to PSMA-targeted radiotherapy. In this work we demonstrate that 67 Cu-CuSarbisPSMA and 177 Lu-LuPSMA I&T provide similar tumor inhibition and increases in survival at equivalent administered activities.…”

“…All animal experiments were performed with the approval of the institutional animal ethics committee. Eight-week old male NSG mice (Australian BioResources, New South Wales) were implanted with LNCaP (human prostate adenocarcinoma) cells as described previously (17). Mice (n=5) bearing subcutaneous LNCaP xenografts (mean tumor volume ~90 mm 3 ) were randomized into five groups and injected intravenously with either vehicle (saline), 67 Cu-CuSarbisPSMA (5 MBq or 30 MBq)…”

“…A Sar derivative conjugated to a somatostatin receptor-targeting peptide, 64 Cu-CuSarTATE, allows acquisition of high-quality images at 24 hours post-injection in patients with NET (16), and its therapeutic pair, 67 Cu-CuSarTATE, is highly efficacious in a NET model (14). We recently reported high tumor uptake and retention of a copper-64-labeled sarcophagine ligand tethered to two lysine-ureido-glutamate functional groups in a PSMA-positive model (17). Here, we evaluate the therapeutic efficacy of its copper-67 labelled pair, 67 Cu-CuSarbisPSMA (Figure 1), in the same PSMApositive tumor model.…”

Robotic surgery using a DROP-IN beta probe – feasibility study with 68Ga-PSMA in prostate cancer specimens

“…In addition, the influence of renal clearance might also be overcome by using β-emitting isotopes that have a longer half-life, allowing the tumor resection to take place after all renal clearance of non-bound tracer is realized, e.g. using alternative PET isotopes such as 64 Cu (t 1/2 = 12.7 hours), or even theranostic isotopes such as 67 Cu (t 1/2 = 2.5 days), 90 Y (t 1/2 = 2.66 days) or 177 Lu (t 1/2 = 6.6 days) (35)(36)(37).…”