Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies

Prostate Cancer Prostatic Dis. 2020 Mar;23(1):38-52. doi: 10.1038/s41391-019-0174-x. Epub 2019 Oct 8.

Abstract

Theranostic principles utilize a molecular biomarker specific for a tumor target, initially for imaging to assess target expression and, if deemed suitable, for targeted therapy. This presents an exciting opportunity for a highly personalized treatment strategy in the era of precision medicine. Prostate-specific membrane antigen (PSMA) theranostics has attracted increasing attention as a promising targeted treatment in metastatic prostate cancer (PC). 177Lu-DOTA-PSMA-617 (177Lu-PSMA-617) is a PSMA-targeted small molecule with favorable properties and is the most extensively investigated PSMA radioligand for radionuclide therapy (RNT) in PC. Since 2014 multiple retrospective studies and more recently a phase II prospective study demonstrated safety and impressive efficacy of 177Lu-PSMA RNT. The evidence generated by these trials led to two currently underway randomized trials in metastatic castrate-resistant PC: TheraP (NCT03392428) and VISION (NCT03511664). While we wait for these pivotal trials to read out, nuclear medicine physicians, medical oncologists, radiation oncologists, and urologists are facing a steep learning curve to master the intricacies and nuances of this novel therapeutic strategy. This review article aims to share and discuss the evolving experience in practical aspects of PSMA theranostics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Combined Modality Therapy
  • Dipeptides / administration & dosage*
  • Disease Management
  • Drug Administration Schedule
  • Follow-Up Studies
  • Heterocyclic Compounds, 1-Ring / administration & dosage*
  • Humans
  • Male
  • Molecular Imaging* / methods
  • Molecular Targeted Therapy* / adverse effects
  • Molecular Targeted Therapy* / methods
  • Neoplasm Staging
  • Patient Selection
  • Positron Emission Tomography Computed Tomography
  • Prognosis
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / therapy*
  • Retreatment
  • Theranostic Nanomedicine* / methods
  • Treatment Outcome

Substances

  • 177Lu-PSMA-617
  • Dipeptides
  • Heterocyclic Compounds, 1-Ring

Associated data

  • ClinicalTrials.gov/NCT03392428
  • ClinicalTrials.gov/NCT03511664