How to cite: Reiter RE. “Emerging Molecular Targeted Imaging Agents.” Grand Rounds in Urology. February 2026. Accessed Apr 2026. https://grandroundsinurology.com/emerging-molecular-targeted-imaging-agents/
Summary
Robert E. Reiter, MD, MBA, Bing Professor of Urologic Oncology and Molecular Biology, University of California, Los Angeles, Los Angeles, California, examines limitations of prostate-specific membrane antigen positron emission tomography (PSMA PET) and reviews emerging molecular targeted imaging agents designed to improve detection sensitivity, address tumor heterogeneity, and expand theranostic applications.
PSMA PET is the most accurate modality for nodal and metastatic staging compared with computed tomography, bone scan, choline, and fluciclovine imaging. Three tracers are approved in the United States, with broadly similar performance characteristics. Despite advances, detection rates remain limited at low prostate-specific antigen (PSA) levels, particularly in biochemical recurrence between 0.2 and 0.5 ng/mL. In addition, 15-30% of tumors exhibit absent or heterogeneous PSMA expression, and lineage plasticity may reduce target expression.
Dual tracer imaging with fluorodeoxyglucose or other agents can highlight discordant disease and identify patients unlikely to benefit from PSMA-directed radioligand therapy.
Copper-64/67-SAR-bisPSMA is presented as a promising next-generation radiometal tracer. Copper-64 enables delayed imaging due to tumor retention, with improved lesion conspicuity at 24 hours and reduced bladder activity. In the COBRA trial, 70% of patients had positive scans at same-day imaging, increasing to 90 percent at 24 hours. The prospective Co-PSMA comparative trial met its primary endpoint for improved detection compared with gallium-68 PSMA in men with low PSA biochemical recurrence.
Additional emerging targets include STEAP1/2, prostate stem cell antigen, hexokinase 2, B7-H3, Trop-2, CEACAM5, and DLL3. Antibody and minibody platforms, including zirconium-89–labeled constructs, demonstrate feasibility for subtype-specific imaging.
Molecular targeted imaging is evolving beyond PSMA toward subtype-directed precision imaging.
The International Prostate Cancer Update (IPCU), is a multi-day, CME-accredited conference focused on new developments in prostate cancer treatment, diagnosis, and prevention. IPCU 36 featured lectures, interactive discussions, panel roundtables, debates, and case reports. This conference is led by expert physicians and is designed for urologists, medical oncologists, radiation oncologists, and other healthcare professionals involved in the diagnosis and treatment of prostate cancer.
The goal of this educational program is to equip healthcare professionals involved in the diagnosis and treatment of prostate cancer with the up-to-date clinical knowledge and tools they need to best treat their patients. The program will discuss the treatment of prostate cancer from diagnosis to treating advanced and metastatic disease. The conference aims to give physicians exposure to a comprehensive review of treating prostate cancer patients and to give them a chance to discuss the issues with peers and experts.
ABOUT THE AUTHOR
Robert E. Reiter, MD, MBA, is the Bing Professor of Urologic Oncology and a Professor of Molecular Biology at the University of California, Los Angeles. Dr. Reiter also serves as the Director of the Prostate Cancer Program and of Urologic Research, as Chief of the Division of Urologic Oncology, and as Co-Director of the Genitourinary Oncology Program for the Jonsson Cancer Center at the University of California, Los Angeles. He is an internationally recognized expert in all areas of prostate cancer management and research. Dr. Reiter has a particular interest in the multidisciplinary management of men with high-risk prostate cancer, incorporating the latest in genomics, clinical trials, and precision medical therapies into treatment plans.
