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Strand J, Nordeman P, Honarvar H, et al. Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity. ChemistryOpen. 2015;4(2):174-82doi: 10.1002/open.201402097.
Strand, J., Nordeman, P., Honarvar, H., Altai, M., Orlova, A., Larhed, M., & Tolmachev, V. (2015). Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity. ChemistryOpen, 4(2), 174-82. https://doi.org/10.1002/open.201402097
Strand, Joanna, et al. "Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity." ChemistryOpen vol. 4,2 (2015): 174-82. doi: https://doi.org/10.1002/open.201402097
Strand J, Nordeman P, Honarvar H, Altai M, Orlova A, Larhed M, Tolmachev V. Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity. ChemistryOpen. 2015 Apr;4(2):174-82. doi: 10.1002/open.201402097. Epub 2015 Jan 12. PMID: 25969816; PMCID: PMC4420590.
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ChemistryOpen. 2015 Apr;4(2):174-82. doi: 10.1002/open.201402097. Epub 2015 Jan 12.

Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity.

ChemistryOpen

Joanna Strand, Patrik Nordeman, Hadis Honarvar, Mohamed Altai, Anna Orlova, Mats Larhed, Vladimir Tolmachev

Affiliations

  1. Biomedical Radiation Sciences, Faculty of Medicine, Uppsala University 751 85, Uppsala, Sweden.
  2. Preclinical PET Platform, Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University 751 23, Uppsala, Sweden.

PMID: 25969816 PMCID: PMC4420590 DOI: 10.1002/open.201402097

Abstract

Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of (125)I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using (125)I-IPEM with an overall yield of 45±3 %. (125)I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of (125)I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g(-1)at 1 and 4 h after injection, respectively) was significantly lower than uptake of (125)I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g(-1)at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity.

Keywords: affibody molecules; drug design; iodophenethylmaleimide; radiolabeling; radiopharmaceuticals

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