PSMA-targeted NIR probes for image-guided detection of prostate cancer

Agostino Cilibrizzi, Julie Tzu Wen Wang, Siham Memdouh, Antonella Iacovone, Kate McElroy, Noor Jaffar, Jennifer Denise Young, Robert C. Hider, Philip Blower, Khuloud Al-Jamal, Vincenzo Abbate

Research output: Contribution to journalArticlepeer-review

Abstract

Tumour-targeted near-infrared (NIR) optical imaging is an emerging tool for the detection of malignant tissues. This modality can be useful in both diagnosis and intraoperative visualisation, to help defining tumour margins and allow a more precise removal of all the cancerous mass during surgery. In this context, we have developed a series of NIR fluorescent probes that target the prostate-specific membrane antigen (PSMA), an established biomarker overexpressed in prostate cancer. Four new NIR imaging agents were prepared by conjugating the well-known urea-based PSMA targeting module to the NIR fluorophore Cy7.5, with linkers of 7, 10, 17 and 24 atoms. The affinity of each probe for PSMA was assessed through competitive binding and IC50 measurement in prostate cancer cells, using a previously reported PSMA-targeted NIR probe (i.e. PSMA-IRDye800CW) as reference. The NIR probe PSMA-Cy7.5_2 demonstrated a high affinity for PSMA (i.e. IC50 = 58.8 nM) and was further studied in mouse xenograft models of prostate cancer, to assess its ability to image PSMA positive tumour tissues. While PSMA-Cy7.5_2 out-performed PSMA-IRDye800CW in vitro, its tumour accumulation in vivo was not as evident. Further micellar aggregation studies indicated that the relatively higher hydrophobic property of PSMA-Cy7.5_2 may lower its bioavailability and tissue distribution following systemic injection, limiting its ability of targeting PSMA tumour in vivo. Nevertheless, the excellent binding capability of PSMA-Cy7.5_2 renders this probe a valid lead for further structural optimisation to develop imaging analogues with high affinity and specificity for PSMA, as required for effective NIR fluorescence-guided applications pre-clinically and clinically.

Original languageEnglish
Article number112734
JournalColloids and Surfaces B: Biointerfaces
Volume218
Early online date28 Jul 2022
DOIs
Publication statusPublished - 31 Oct 2022
Externally publishedYes

Keywords

  • Image-guided detection
  • in vivo imaging
  • Near-infrared probes
  • Optical imaging
  • Prostate cancer
  • Prostate-specific membrane antigen

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

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