Development of a I-124-labeled version of the anti-PSMA monoclonal antibody capromab for immunoPET staging of prostate cancer: Aspects of labeling chemistry and biodistribution
2014 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 44, no 6, 1998-2008 p.Article in journal (Refereed) Published
Correct staging of prostate cancer is an unmet clinical need. Radionuclide targeting of prostate-specific membrane antigen (PSMA) with In-111-labeled capromab pendetide (ProstaScint) is a clinical option for prostate cancer staging. We propose the use of I-124-labeled capromab to decrease the retention of radioactivity in healthy organs (due to the non-residualizing properties of the radiolabel). The use of I-124 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 I-125/In-111-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 I-124-capromab.
Place, publisher, year, edition, pages
2014. Vol. 44, no 6, 1998-2008 p.
prostate cancer, iodine-124, PET, molecular imaging, prostate-specific membrane antigen
Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-229969DOI: 10.3892/ijo.2014.2376ISI: 000338694200023PubMedID: 24718894OAI: oai:DiVA.org:uu-229969DiVA: diva2:738655
FunderSwedish Research CouncilSwedish Cancer Society