Effect of Holmium-166 Injection into Hepatocellular Carcinomas (SK-HEP1) Heterotransplanted in Mice

ABSTRACT

PURPOSE: Holmium-166(H0-166) is a potent beta-emitter with a short half-life(26.83 hours) and high betaenergy(1.85MeV), and its necrotic effect on breast carcinoma has been proved. In cases of hepatocellularcarcinoma, Ho-166 can therefore be used for internal radiation therapy. The purpose of this study is to evaluatethe therapeutic effect of Ho-166 on hepatocellular carcinomas and to estimate the required dosage, according totheir size. MATERIALS AND METHODS: Tumor cells of hepatocellular carcinomas(SK-HEP1) were subcutaneouslyheterotransplanted into 71 nude mice and 71 hepatocellular carcinomas less than 2cm in diameter were grown. Ho-166was directly injected into a tumor at a dosage of between 0.5mCi(18.5MBq) and 3.0mCi(11MBq). After initialinjection of Ho-166, tumor uptake and radioactivity were indicated by gamma camera scanning. Hepatocellularcarcinomas in a control group of 20 mice were injected with 0.025ml of normal saline(n=10) and chitosansolution(n=10). Pathologic examination was performed and the necrotic tumor area was measured with an imageanalyzer. RESULTS: All specimens of Ho-166-injected hepatocellular carcinomas showed coagulation necrosisconsistent with radiation effect, while the control group did not show necrosis. As the injected dosage of Ho-166was increased, the necrotic area extended proportionally and the dosage required for total necrosis was calculatedaccording to tumor size. Gamma scintigraphy showed that injected Ho-166 had accumulated within the tumor, withoutthe accumulation of radioactivity in other organs ; the required dosage could be predicted on the basis ofradioactivity count indicated by a gamma camera. CONCLUSION: High-energy beta radiation emitted by Ho-166 can besufficient to kill tumor tissue without associated radiation damage to neighboring organs; intratumoral injectionis thought to be a promising therapeutic approach and a new method for the treatment of hepatocellular carcinoma.