Radiolabeling efficiency and stability study on Lutetium-177 labeled bombesin peptide

Abstract

Bombesin is a 14-amino-acid peptide having the ability to specifically bind gastrin releasing peptide receptors (GRPR) which show over-expression in many types of cancer cells. Therefore, bombesin analogs have been complexed with radionuclides and reported as radiopharmaceuticals for cancer diagnosis and therapy. Lutetium-177 (Lu-177) is a beta emitting radionuclide that decays with a half-life of 6.65 days. The medium beta energy and the relatively long half-life of Lu-177 make it one of the ideal radionuclides used in targeted radionuclide therapy. As the oxidation state of this radioisotope is 3+, it requires multidentate chelators such as DOTA to form stable complex. In this work, the commercially available conjugated peptide, DOTA-[Pro1, Tyr4]-bombesin, was labeled with Lu-177 for preliminary formulation as a therapeutic radiopharmaceutical. The aim was to evaluate the radiolabeling efficiency using various amounts of the peptide and the stability in human serum for 7 days. The radiolabeling was performed in sterile water for injection with 5 mCi of Lu-177, adjusted to pH 5.5 to 6.0 by 0.5 M sodium acetate, and incubated at 100°C for 30 min. It was found that the radiochemical yield was more than 99% when using 20 µg of the peptide, and the complex was stable for a week. Moreover, human serum was used to simulate in vivo condition. The results showed high complex stability with more than 98% remaining intact after 7 days.