TY - JOUR
T1 - Development of a 124I-labeled version of the anti-PSMA monoclonal antibody capromab for immunoPET staging of prostate cancer
T2 - Aspects of labeling chemistry and biodistribution
AU - Tolmachev, Vladimir
AU - Malmberg, Jennie
AU - Estrada, Sergio
AU - Eriksson, Olof
AU - Orlova, Anna
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
KW - Iodine-124
KW - Molecular imaging
KW - PET
KW - Prostate cancer
KW - Prostate-specific membrane antigen
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U2 - 10.3892/ijo.2014.2376
DO - 10.3892/ijo.2014.2376
M3 - Article
C2 - 24718894
AN - SCOPUS:84899535976
VL - 45
SP - 1998
EP - 2008
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 6
ER -