Experimental and Clinical Studies on the Intraarterial Injection of Holmium-166 Chitosan Complex in the Treatment of Hepatocellular Carcinoma

PURPOSE: The purposes of this study were to evaluate the biodistribution and effect of Ho-166 radionuclide by intra-arterial injection of the Ho-166 chitosan complex in dogs and to assess the clinical efficacy and side effects of this complex in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In an experimental study, 20 mCi of Ho-166 chitosan complex was injected into the left hepatic artery of six adult dogs. The distribution of radioactivity in each organ was calculated using a gamma camera scan at regular intervals. A beta ray radioactivity count (cpm) of blood and urine was performed periodically, and hematologic and hepatic function were regularly assessed. At 4, 8 and 12 weeks after intra-arterial injection, bone marrow and liver were pathologically evaluated. Twenty-five patients with a single, nodular HCC mass 3 -9 cm in diameter were treated by intra-arterial injection of Ho-166 chitosan complex, and immediately after the procedure a gamma camera scan was obtained. A beta ray radioactivity count(cpm) of blood was performed periodically, hematologic and hepatic function were regularly evaluated, and CT scans and angiograms were obtained 3 months after the procedure. On the basis of the CT and angiographic findings, the treatment effects were classified as complete (CR), partial (PR) or non-response(NR). RESULTS: In the animal study, blood radioactivity peaked immediately after injection and then declined rapidly. Urinary excretion was 0.17%. The proportion of radioactivity in each organ per whole body was 25% in the left lobe of the liver, 7% in the right lobe, 3% in the lung, 1.4 -3% in the bladder, and 2% in bone. WBC and platelet counts declined maximally at 3 -4 weeks and recovered at 12 weeks. The cellularity of bone marrow was 25% at 4 weeks and 55% at 12 weeks, findings which correlated well with the observed hematologic changes. In the clinical study of 25 HCC patients, CR was achieved in 17 (68%) cases, PR in 5 (20%) and NR in 3 (12%). At gamma camera imaging immediately after treatment, tumor radioactivity was localized in 76% of cases. In six cases (24%) WBC and platelet counts decreased 50% or more compared with their pretreatment level. In 67 -75% of cases, SGOT and SGPT were, within 1 -3 days, 2 -3 times higher than their pre-treatment level, and recovered at post 4 weeks. CONCLUSION: Ho-166 chitosan complex administrated intra-arterially localized the target organ with minimal side effects, and we therefore suggest that it may be used in the treatment of nodular and hypervascular HCC. Further study of its dosimetry and possible hematologic side reactions is needed, however.