Development of a 124I-labeled version of the anti-PSMA monoclonal antibody capromab for immunoPET staging of prostate cancer: Aspects of labeling chemistry and biodistribution

Int J Oncol. 2014 Jun;44(6):1998-2008. doi: 10.3892/ijo.2014.2376. Epub 2014 Apr 10.

Abstract

Correct staging of prostate cancer is an unmet clinical need. Radionuclide targeting of prostate-specific membrane antigen (PSMA) with 111In-labeled capromab pendetide (ProstaScint) is a clinical option for prostate cancer staging. We propose the use of 124I-labeled capromab to decrease the retention of radioactivity in healthy organs (due to the non-residualizing properties of the radiolabel). The use of 124I as a label should increase imaging sensitivity due to the advantages of PET as an imaging modality. Capromab targets the intracellular domain of PSMA; accumulation of radioactivity in the tumor should not depend on internalization of the antigen/antibody complex. Capromab was iodinated, and its targeting properties were compared with indium labeled counterpart in LNCaP xenografts in dual isotope mode. PSMA-negative xenografts (PC3) were used as a negative control. Radioiodinated capromab bound to PSMA specifically. Biodistribution of 125I/111In-capromab showed a more rapid clearance of iodine radioactivity from liver, spleen, kidneys, bones, colon tissue, as well as tumors. Maximum tumor uptake (13±8% ID/g for iodine and 29±9% ID/g for indium) and tumor-to-non-tumor ratios for both agents were measured 5 days post-injection (pi). High tumor accumulation and low uptake of radioactivity in normal organs were confirmed using microPET/CT 5 days pi of 124I-capromab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antigens, Surface / metabolism
  • Cell Line, Tumor
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Iodine Radioisotopes / chemistry*
  • Iodine Radioisotopes / pharmacokinetics*
  • Isotope Labeling
  • Lymphatic Metastasis / diagnostic imaging*
  • Lymphatic Metastasis / pathology
  • Male
  • Mice
  • Neoplasm Staging / methods
  • Neoplasms, Experimental
  • Positron-Emission Tomography
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / secondary
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Iodine Radioisotopes
  • Capromab Pendetide
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II