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.
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.
Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Vladimir
V
Tolmachev
Preclinical PET Platform, Uppsala University, Uppsala, Sweden.
Jennie
J
Malmberg
Preclinical PET Platform, Uppsala University, Uppsala, Sweden.
Sergio
S
Estrada
Preclinical PET Platform, Uppsala University, Uppsala, Sweden.
Olof
O
Eriksson
Preclinical PET Platform, Uppsala University, Uppsala, Sweden.
Anna
A
Orlova
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000493:pharmacokinetics*; D000954:Antigens, Surface / Q000378:metabolism; D045744:Cell Line, Tumor; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D051379:Mice; D009367:Neoplasm Staging / Q000379:methods; D009374:Neoplasms, Experimental; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000556:secondary; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007457:Iodine Radioisotopes; C101315:Capromab Pendetide; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II