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.

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.

• Authors: Vladimir Tolmachev, Jennie Malmberg, Sergio Estrada, Olof Eriksson, Anna Orlova
• Journal: International journal of oncology (Int J Oncol) Vol. 44 Issue 6 Pg. 1998-2008 (Jun 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 24718894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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