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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. (Orlova)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
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2014 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 44, no 6, 1998-2008 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
prostate cancer, iodine-124, PET, molecular imaging, prostate-specific membrane antigen
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-229969DOI: 10.3892/ijo.2014.2376ISI: 000338694200023PubMedID: 24718894OAI: oai:DiVA.org:uu-229969DiVA: diva2:738655
Funder
Swedish Research CouncilSwedish Cancer Society
Available from: 2014-08-18 Created: 2014-08-18 Last updated: 2017-12-05Bibliographically approved

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Tolmachev, VladimirMalmberg, JennieEstrada, SergioEriksson, OlofOrlova, Anna

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