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Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.ORCID iD: 0000-0001-6120-2683
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Avdelningen för sjukhusfysik.
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2007 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 19, no 3, 485-493 p.Article in journal (Refereed) Published
Abstract [en]

The use of radionuclide molecular imaging enables the selection of patients for treatment using molecular medicine. Preclinical studies have demonstrated that a novel low-molecular-weight affinity ligand, Affibody molecule Z(HER2:342) can image the expression of HER2 with high sensitivity and specificity in tumour xenografts and has a potential for the selection of patients for treatment using Herceptin or other anti-HER2 medicine. In this study, we performed a comparative evaluation of two possible linkers for radioiodination of the Affibody molecule Z(HER2:342), 4-iodobenzoate (PIB) and [4-isothiocyanatobenzyl)-amino]-undecahydro-closo-dodecaborate (DABI). It was shown that the use of DABI makes it possible to obtain radioiodinated Z(HER2:342) with preserved capacity for selective binding to HER2-expressing cells. There was no difference between 125I-PIB-Z(HER2:342) and 125I-DABI-Z(HER2:342) in cellular retention of radioactivity after interrupted incubation with radiolabelled Affibody ligands. In vivo, the biodistribution of 125I-PIB-Z(HER2:342) was characterized by a high tumour uptake at 4 h pi (12.7+/-4.6% IA/g) and a quick clearance from blood and normal organs. The tumour uptake of 125I-DABI-Z(HER2:342) was appreciably lower (2.7+/-1.2% IA/g), and a high uptake of this conjugate in the liver was observed. A gamma-camera experiment (at 6 h pi) demonstrated that the use of 125I-PIB-Z(HER2:342) provided a much better contrast of imaging HER2-expressing xenografts than the use of 125I-DABI-Z(HER2:342). In conclusion, 125I-PIB-Z(HER2:342) is superior to 125I-DABI-Z(HER2:342) as an agent for imaging HER2 expression in vivo.

Place, publisher, year, edition, pages
2007. Vol. 19, no 3, 485-493 p.
Keyword [en]
Affinity Labels, Animals, Benzoates/chemistry/*metabolism/pharmacokinetics, Biological Availability, Boron Compounds/chemistry/*metabolism/pharmacokinetics, Cell Line; Tumor, Humans, Iodine Radioisotopes, Ligands, Mice, Mice; Inbred BALB C, Radionuclide Imaging, Receptor; erbB-2/*metabolism, Whole Body Imaging, Xenograft Model Antitumor Assays
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-17051ISI: 000244233000020PubMedID: 17273798OAI: oai:DiVA.org:uu-17051DiVA: diva2:44822
Available from: 2008-06-16 Created: 2008-06-16 Last updated: 2017-12-08Bibliographically approved

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Tran, ThuyOrlova, AnnaSandström, MattiasTolmachev, Vladimir

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Biomedical Radiation SciencesAvdelningen för sjukhusfysikDepartment of Medical Sciences
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