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Targeting Free Prostate-Specific Antigen for In Vivo Imaging of Prostate Cancer Using a Monoclonal Antibody Specific for Unique Epitopes Accessible on Free Prostate-Specific Antigen Alone.

Author:
  • Susan Evans Axelsson
  • David Ulmert
  • Anders Örbom
  • Pernilla Peterson
  • Olle Nilsson
  • Johan Wennerberg
  • Joanna Strand
  • Karin Wingårdh
  • Tomas Olsson
  • Zandra Hagman
  • Vladimir Tolmachev
  • Anders Bjartell
  • Hans Lilja
  • Sven-Erik Strand
Publishing year: 2012
Language: English
Pages: 243-251
Publication/Series: Cancer Biotherapy & Radiopharmaceuticals
Volume: 27
Issue: 4
Document type: Journal article
Publisher: Mary Ann Liebert, Inc.

Abstract english

This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected (125)I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting (125)I-labeled PSA30. Tissue uptake of (125)I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, (18)F-fluoro-deoxy-glucose ((18)F-FDG) or (18)F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high (125)I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either (18)F-FDG or (18)F-choline. Biodistribution of (125)I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24-48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.

Keywords

  • Cancer and Oncology

Other

Published
  • Urological cancer, Malmö
  • Clinical Chemistry, Malmö
  • Medical Radiation Physics, Malmö
  • ISSN: 1557-8852
Sven-Erik Strand
E-mail: sven-erik [dot] strand [at] med [dot] lu [dot] se

Project manager

Systemic Radiation Therapy Group

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Professor emeritus

Medical Radiation Physics, Lund

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