Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand
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
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.
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
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-17051ISI: 000244233000020PubMedID: 17273798OAI: oai:DiVA.org:uu-17051DiVA: diva2:44822