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.