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Comparative biodistribution of the radiohalogenated (Br, I and At) antibody A33: Implications for in vivo dosimetry
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (BMS)ORCID iD: 0000-0001-6120-2683
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (BMS)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (BMS)
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2002 (English)In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, Vol. 17, no 4, 385-96 p.Article in journal (Refereed) Published
Abstract [en]

The alpha-emitter astatine-211 (T(1/2) = 7.2 h) has great potential for use in targeted radionuclide therapy. Its potent alpha-radiation makes (211)At unsuitable for dose planning. Its x-rays can be used for gamma-camera monitoring of the radioactivity distribution during therapy but not for accurate estimation of absorbed dose in critical organs. This study was intended to establish whether the absorbed dose delivered by astatinated antibody could be accurately determined by analogue labeling with radiohalogens, better suited for quantitative measurements in vivo. PET facilitates quantitative pharmacokinetics; possible halogen labels are, e.g., (76)Br (T(1/2) = 16.2 h) and (124)I (T(1/2) = 4.18 d). Antibody A33 was labeled with (76)Br, (125)I and (211)At using N-succinimidyl-p-halobenzoates. The conjugates were co-injected into Sprague-Dawley rats. Radioactivity concentrations in different organs and tissues were measured at three time points. Pharmacokinetic data were used to calculate absorbed doses. (125)I and (76)Br reflected the biokinetics of astatine reasonably well. The absorbed doses in bladder, kidney, pancreas, liver, bone and brain were determined with 10% accuracy. The absorbed doses in stomach, spleen and thyroid were underestimated by a factor 2-3. Positron-emitting analogues can be used to predict the astatine-derived dose in critical organs. Correction factors should be used for stomach, spleen and thyroid.

Place, publisher, year, edition, pages
2002. Vol. 17, no 4, 385-96 p.
Keyword [en]
Animals, Antibodies; Monoclonal/*pharmacokinetics, Astatine/*pharmacokinetics, Bromine Radioisotopes/*pharmacokinetics, Comparative Study, Iodine Radioisotopes/*pharmacokinetics, Male, Radioimmunotherapy, Radiometry, Rats, Rats; Sprague-Dawley, Research Support; Non-U.S. Gov't, Tissue Distribution, Tomography; Emission-Computed; Single-Photon
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-73660DOI: 10.1089/108497802760363187PubMedID: 12396703OAI: oai:DiVA.org:uu-73660DiVA: diva2:101570
Available from: 2007-03-14 Created: 2007-03-14 Last updated: 2015-03-24Bibliographically approved

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Orlova, AnnaGedda, LarsLundqvist, HansTolmachev, VladimirSundin, Anders

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