Click chemistry for [99mTc(CO)3] labeling of Lys3-bombesin

99mTc-HYNIC labeled Lys3-bombesin has shown specific binding to gastrin-releasing peptide receptors (GRP-r) over-expressed in cancer cells. Click chemistry offers an innovative functionalization strategy for biomolecules such as bombesin. The aim of this research was to apply a click chemistry approach for [99mTc(CO)3] labeling of Lys3-bombesin and to compare the in vitro MCF7 breast cancer cell uptake and biodistribution profile in mice with that of 99mTc-EDDA/HYNIC-Lys3-bombesin. The results suggest a higher lipophilicity for 99mTc(CO)3-triazole-Lys3-bombesin which explains its higher in vivo hepatobiliary elimination. Pancreas-to-blood ratio for 99mTc(CO)3-triazole-Lys3-bombesin was 4.46 at 3 h and both bombesin radiopharmaceuticals showed specific recognition for GRP receptors in MCF7 cancer cells. Click chemistry is a reliable approach for [99mTc(CO)3] labeling of Lys3-bombesin.