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Novel Radiopharmaceuticals and Future of Theranostics in Genitourinary Cancers

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.

Martina Sollinia,b ∙ Jeremie Calaisc ∙ Arturo Chitia,b ∙ Louise Emmettd,e,f ∙ Stefano Fantig ∙ Wolfgang Fendlerh,i ∙ Ken Herrmannh,i ∙ Thomas A. Hopej,k,l ∙ Oliver Sartorm ∙ Brian Shuchn ∙ Scott Tagawao ∙ Michael S. Hofmanp,q
 
  1. Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, Milano, Italy
  2. IRCCS Nuclear Medicine Department, IRCCS San Raffaele, Milano, Italy
  3. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USA
  4. Department of Theranostics and Nuclear Medicine, St Vincent’s Hospital, Sydney, Australia
  5. St Vincent’s Clinical School, University of New South Wales, Sydney, Australia
  6. Garvan Institute of Medical Research, Sydney, Australia
  7. Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
  8. Department of Nuclear Medicine, West German Cancer Center, University Hospital Essen, Essen, Germany
  9. Cancer Consortium partner site Essen/Düsseldorf, DKFZ and University Hospital Essen, Essen, Germany
  10. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA
  11. Department of Radiology, San Francisco VA Medical Center, San Francisco, CA, USA
  12. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
  13. Department of Oncology, Mayo Clinic, Rochester, MN, USA
  14. Department of Urology, UCLA, Los Angeles, CA, USA
  15. Weill Cornell Medicine, New York, NY, USA
  16. Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  17. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
Source: Sollini, Martina et al. Novel Radiopharmaceuticals and Future of Theranostics in Genitourinary Cancers. European Urology, 2024. DOI: 10.1016/j.eururo.2024.09.036