Prostate-specific membrane antigen-based imaging

Abstract

SUMMARY Prostate cancer (PC) is the most common non-cutaneous malignancy affecting men in North America. Despite significant efforts, conventional imaging of PC does not contribute to patient management as much as imaging performed for other common cancers. Given the lack of specificity in conventional imaging techniques, one possible solution is to screen for PC specific antigenic targets and generate agents able to specifically bind. Prostate specific membrane antigen (PSMA) is over-expressed in PC tissue, with low levels of expression in the small intestine, renal tubular cells and salivary gland. The first clinical agent for targeting PSMA was 111In-capromab, involving an antibody recognizing the internal domain of PSMA. The second- and third-generation humanized PSMA binding antibodies have the potential to overcome some of the limitations inherent to capromab pendetide i.e. inability to bind to live PC cells. One example is the humanized monoclonal antibody J591 (Hu mAb J591) that was developed primarily for therapeutic purposes but also has interesting imaging characteristics including the identification of bone metastases in PC. The major disadvantage of use of mAb for imaging is slow target recognition and background clearance in an appropriate timeframe for diagnostic imaging. Urea-based compounds such as small molecule inhibitors may also present promising agents for PC imaging with SPECT and PET. Two such small-molecule inhibitors targeting PSMA, MIP-1072 and MIP-1095, have exhibited high affinity for PSMA. The uptake of 123I-MIP-1072 and 123I-MIP-1095 in PC xenografts have imaged successfully with favorable properties amenable to human trials. While advances in conventional imaging will continue, Ab and small molecule imaging exemplified by PSMA targeting have the greatest potential to improve diagnostic sensitivity and specificity.

Management of Biochemical Recurrence After Primary Treatment of Prostate Cancer: A Systematic Review of the Literature

“…Studies have shown variable efficacy in PCa detection using ProstaScint, with average positive and negative predictive values of 60% and 70%, respectively [26]. However, this tracer binds to the intracellular domain of PSMA and thereby detects only necrotic tissue, having limited ability to detect viable cancer, including bone metastasis, giving it a high false-negative rate and limited applicability in the setting of recurrent disease [27].…”

Preclinical Comparison of Al18F- and 68Ga-Labeled Gastrin-Releasing Peptide Receptor Antagonists for PET Imaging of Prostate Cancer

“…However, their application is most valuable in late-stage, recurrent, or metastatic PCa. Increasing efforts are being made in developing PET imaging agents targeting specific biomarkers of PCa, such as gastrin-releasing peptide receptor (GRPR) (5) and prostate-specific membrane antigen (6).…”

New Radiopharmaceuticals Based on Prostate-Specific Inhibitors of Membrane Antigen for Diagnostics and Therapy of Metastatic Prostate Cancer

“…Для стадии Т 2 диагностическая точ-ность нативной МРТ составляет не более 58%. Кроме того, методы анатомической визуализации (КТ, МРТ, МР-спектроскопия) имеют низкую чувствительность и специфичность при обнаружении метастатического РПЖ с метастазами в лимфатические узлы и другие мягкие ор-ганы и ткани [1,5,11].…”

“…В отличие от ПСА, ПСМА не обнаруживается в крови. Таким образом, ПСМА является идеальным маркером клеток РПЖ и прекрасной целью для радионуклидной визуализации и терапии [11,13,15].…”