Novel Radiopharmaceuticals and Future of Theranostics in Genitourinary Cancers.
Review
Overview
abstract
BACKGROUND AND OBJECTIVE: This review aims to provide an overview of novel diagnostic and therapeutic radiopharmaceuticals tested recently or used currently in genitourinary cancers within prospective phase 1-2 clinical trials, summarizing progresses and future directions. METHODS: A systematic search was conducted using the PubMed/MEDLINE and ClinicalTrials.gov databases for original prospective research studies following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. KEY FINDINGS AND LIMITATIONS: Forty-six papers were systematically reviewed; 74 ongoing clinical trials were identified. The results of 27 novel radiopharmaceuticals (ie, not approved by the Food and Drug Administration/European Medicines Agency and not listed in the Pharmacopeia) prospectively investigated in genitourinary cancers, mostly prostate, for diagnostic, theranostic, or therapeutic purposes (21, one, and five of the 27 radiopharmaceuticals, respectively) over the past 5 yr were presented. Most were prostate-specific membrane antigen-targeting agents (17/27); other targets included gastrin-releasing peptide receptor, carbonic anhydrase IX, Cu, six transmembrane epithelial antigen of the prostate 1, tumor-associated glycoprotein 42, and urokinase-type plasminogen activator receptor. Ongoing research confirms the same trend. Fibroblast activation protein inhibitor, PD-L1, CD8, nectin-4, and HER2 are other targets under investigation. Among the 22 ongoing therapeutic trials (out of the 74 ongoing clinical trials), targeted alpha therapy is being explored in 12, and five are evaluating combinations of radioligand therapy with other treatments. We confirmed the safety of radiopharmaceuticals (regardless of the diagnostic/therapeutic purpose) and showed promising results in terms of diagnostic accuracy and therapeutic efficacy in genitourinary cancers. CONCLUSIONS AND CLINICAL IMPLICATIONS: There continues to be expansion in radiopharmaceutical approaches to genitourinary cancers, reflecting a strong emphasis on improving tumor detection and treatment, which will likely impact future management across the disease spectrum, with the potential for improved patient care and outcomes.
