Magnetic Resonance Imaging of PSMA-Positive Prostate Cancer by a Targeted and Activatable Gd(III) MR Contrast Agent

Hao Li, Dong Luo, Chaonan Yuan, Xinning Wang, Jing Wang, James P. Basilion*, Thomas J. Meade

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed in aggressive prostate cancer (PCa) and has been extensively studied as a PCa diagnostic imaging biomarker. Multiple imaging modalities have exploited PSMA as a biomarker including magnetic resonance (MR), Optical, and PET imaging. Of all the imaging MR imaging provides the most detailed information, concurrently providing anatomical, functional, and potentially molecular information. However, the lower sensitivity of MR requires development of molecular MR contrast agents that provides high signal-to-noise ratios. Herein, we report the first targeted and activatable Gd(III)-based MR contrast agents prostate cancer probe 1 and 2 (PCP-1 and -2). We successfully used PCP-2 to differentiate between PSMA+ and PSMA- prostate cancer cells with both in vitro fluorescence imaging and in vivo MR imaging. The in vivo MR imaging results were further supported by ex vivo fluorescence imaging studies, showcasing the unique bimodal feature of PCP-2. Furthermore, PCP-2 highlights a unique molecular MR probe design strategy that improved the sensitivity of traditional biomarker-targeted MR imaging, addressing a critical unmet need in molecular MR imaging field. This work represents the first example of a targeted and activatable MR contrast agent that can be systemically administered in vivo to highlight PSMA+ prostate tumors, paving the way for the clinical translation of MR PSMA imaging.

Original languageEnglish (US)
Pages (from-to)17097-17108
Number of pages12
JournalJournal of the American Chemical Society
Volume143
Issue number41
DOIs
StatePublished - Oct 20 2021

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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