Preclinical pharmacokinetic, biodistribution, radiation dosimetry, and toxicity studies of 99mTc-HYNIC-(Ser)3-LTVPWY: A novel HER2-targeted peptide radiotracer

Accurate assessment of the HER2 expression is an essential issue for predicting response to anti-HER2 therapy in breast cancer patients. The aim of this study was to evaluate Tc-99m-HYNIC-(Ser)(3)-LTVPWY (Tc-99m-HYNIC-LY) peptide as a novel HER2-targeted radiolabeled peptide in healthy mice to examine the applicability of this imaging agent in a first-in-human clinical trial. To this end, pharmacokinetic and dosimetry studies were performed according to the ICH guideline M3 (R2) with Tc-99m-HYNIC-LY. To estimate the radiation-absorbed doses in humans, the accumulated activity in each mouse organ was calculated based on biodistribution data. In addition, toxicology assessment was performed based on mortality events, body weights, and serum biochemical, hematological, and histopathological assays. The pharmacokinetic study showed rapid blood clearance. Based on the results of biodistribution study, the highest radioactivity was observed in the kidneys. The projected absorbed doses to the kidneys, liver, lungs, stomach, and spleen were obtained as 1.70E-02, 1.42E-02, 1.02E-02, 8.62E-03, and 8.34E-03 mSv/MBq, respectively. The results also revealed that serum biochemical and hematological parameters were in the normal range. No significant morphologic alterations were observed in the liver, kidneys, and spleen tissues. Consequently, the results were indicative of the suitability of Tc-99m-HYNIC-LY peptide for advancement to a first-in-human clinical trial.