Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand

  • Authors:
    • Thuy Tran
    • Anna Orlova
    • Igor Sivaev
    • Mattias Sandström
    • Vladimir Tolmachev
  • View Affiliations

  • Published online on: March 1, 2007     https://doi.org/10.3892/ijmm.19.3.485
  • Pages: 485-493
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Abstract

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 ZHER2:342 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 ZHER2:342, 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 ZHER2:342 with preserved capacity for selective binding to HER2-expressing cells. There was no difference between 125I-PIB-ZHER2:342 and 125I-DABI-ZHER2:342 in cellular retention of radioactivity after interrupted incubation with radiolabelled Affibody ligands. In vivo, the biodistribution of 125I-PIB-ZHER2:342 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-ZHER2:342 was appreciably lower (2.7±1.2% IA/g), and a high uptake of this conjugate in the liver was observed. A γ-camera experiment (at 6 h pi) demonstrated that the use of 125I-PIB-ZHER2:342 provided a much better contrast of imaging HER2-expressing xenografts than the use of 125I-DABI-ZHER2:342. In conclusion, 125I-PIB-ZHER2:342 is superior to 125I-DABI-ZHER2:342 as an agent for imaging HER2 expression in vivo.

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March 2007
Volume 19 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tran T, Orlova A, Sivaev I, Sandström M and Tolmachev V: Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand. Int J Mol Med 19: 485-493, 2007
APA
Tran, T., Orlova, A., Sivaev, I., Sandström, M., & Tolmachev, V. (2007). Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand. International Journal of Molecular Medicine, 19, 485-493. https://doi.org/10.3892/ijmm.19.3.485
MLA
Tran, T., Orlova, A., Sivaev, I., Sandström, M., Tolmachev, V."Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand". International Journal of Molecular Medicine 19.3 (2007): 485-493.
Chicago
Tran, T., Orlova, A., Sivaev, I., Sandström, M., Tolmachev, V."Comparison of benzoate- and dodecaborate-based linkers for attachment of radioiodine to HER2-targeting Affibody ligand". International Journal of Molecular Medicine 19, no. 3 (2007): 485-493. https://doi.org/10.3892/ijmm.19.3.485