Effects of 166Holmium and 166Holmium-chitosan Complex(166Ho-CHICO) on Normal Brain of Rats

Abstract

Objectives: We performed an in vivo experiment to investigate the effect of 166Holmium and 166Holmium-chitosan complex(166Ho-CHICO) on the normal brain of rats and to determine the sublethal dose of 166Ho-CHICO. Materials and Methods: 166Ho is a beta and gamma ray emitter. 166Ho-CHICO is a novel radio-pharmaceutical complex with chitosan to facilitate the transport of 166Ho obtained from Korea Atomic Energy Research Center(Taejon, Korea). It is in acidic form and becomes gel state at alkaline pH. One hundred and seventy consecutive rats were divided into four groups：166Ho treated(n＝50), 166Ho-CHICO treated(n＝57), saline treated(n＝5) and chitosan treated(n＝5) groups. 166Ho and 166Ho-CHICO were injected into the rat brain stereotactically with various doses of 0.1mCi/20μl, 0.2mCi/20μl, 0.3mCi/20μl, and 0.4mCi/20μl using an automated microinjector. Nuclear imaging, histopathological and hematological studies were performed in 10 rats in each group at 1 day, 3days, 7 days, 1 month and 3 months after the injections. Results: An infiltration of inflammatory cells and necrotic changes were noted in 166Ho treated group at 1 week after the injection. A wedge-shaped tissue defect due to necrosis, lined with infiltrated glial cells in 166Ho treated group and a cystic defect lined with reactive astroglial cells in 166Holmium-CHICO treated group at 3 months after the injection were observed. 166Ho alone without chitosan leaked out and caused necrotic lesion on the cerebral surface but 166Holmium-CHICO treated group did not show this feature. As the dose of 166Ho increased, the mortality rates were also increased. The mortality rate of the 166Holmium-CHICO group was higher than the 166Ho treated group at a dose of 0.4mCi/20μl/300g. There was no detectable radioactivity due to the leakage or extravasation from the injected site of the brain on the scintigraphy performed at 1 hour, 24 hours and 48 hours after the injection. There was also no detectable activity of 166Holmium-CHICO in other organs including spleen, liver and kidney. Conclusions: 166Ho-CHICO did not leak out to the critical cortical surface of the brain from the injection site and induced radiation changes of the parenchyma around the injection site without cortical damage. The sublethal dose of 166Ho-CHICO for the normal brain in rats was determined to be 0.2mCi/20μl/300g.