Site-specific radioiodination of HER2-targeting affibody molecules using 4-iodophenethylmaleimide decreases renal uptake of radioactivity

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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 125I-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 125I-IPEM with an overall yield of 45±3 %. 125I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of 125I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g-1at 1 and 4 h after injection, respectively) was significantly lower than uptake of 125I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g-1at 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.

Original languageEnglish
Pages (from-to)174-182
Number of pages9
JournalChemistryOpen
Volume4
Issue number2
DOIs
Publication statusPublished - 1 Apr 2015
Externally publishedYes

Keywords

  • affibody molecules
  • drug design
  • iodophenethylmaleimide
  • radiolabeling
  • radiopharmaceuticals

ASJC Scopus subject areas

  • Chemistry(all)

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