A Pilot Study of Trans-Arterial Injection of¹⁶⁶Holmium-Chitosan Complex for Treatment of Small Hepatocellular Carcinoma

Abstract

Percutaneous approaches, such as percutaneous ethanol injection and radiofrequency ablation, have been most widely used for hepatocellular carcinoma patients who were not eligible for surgery. New technologies to improve the efficacy are currently needed. 166Holmium is a neutron activated radionuclide, and has several beneficial radiophysical characteristics for internal radiation therapy. 166Holmium-Chitosan complex, in which chitosan is chelated with 166Holmium, was developed as a radiopharmaceutical for cancer therapy. We have conducted a pilot study to evaluate the clinical efficacy of transarterial administration of 166Holmium-Chitosan complex in patients with a single and small (< 3 cm) hepatocellular carcinoma. 166Holmium-Chitosan complex, at a dose of 20 mCi per cm of tumor mass-diameter, was administered through the artery that directly fed the tumor. Twelve patients were treated with a median follow-up duration of 26 (range: 12-61) months. The tumor diameter ranged between 1.5 and 2.5 cm. Ten patients (83%) had complete response and two (17%) had partial response. The median complete response duration was not reached. The median AFP level declined from 83.8 to 8.3 ng/mL within 2 months after treatment. No grade III/IV toxicity was observed. Grade I and II toxicities were observed in four patients (2 abdominal pain, 1 fever, and 1 AST/ALT elevation). No toxic death occurred. This preliminary study shows a promising and durable complete response rate with an acceptable safety profile. Further studies with greater accrual of patients are warranted.

Cutting edge rare earth radiometals: prospects for cancer theranostics

“…166 Ho has seen a wide range of applications in cancer therapy over the last few decades (Shi et al 2017 ). A wide array of therapeutic applications have been investigated with pre-clinical and clinical trials and studies being reported for radiopharmaceutical therapies for bone marrow cancer (Bayouth et al 1995a , b ; Giralt et al 2003 ; Christoforidou et al 2017 ), metastatic bone pain palliation (Voorde et al 2019 ; Bahrami-Samani et al 2010 ), brain cancer (Huh et al 2005 ; Ha et al 2013 ), liver cancer (Cho et al 2005 ; Kim et al 2006 ), and prostate cancer (Seong et al 2005 ; Kwak et al 2005 ), among others. This radionuclide has gained attention for its potential theranostic applications due to its favourable decay characteristics that allow for its use as both a therapeutic agent and an imaging agent (Tan et al 2020 ).…”

Radiochemical and biological evaluation of novel 153Sm/166Ho‐amino acid–chitosan complexes

“…[16][17] Following these results, 166 Ho-chitosan (DW-166HC) has been approved in Korea as a radiopharmaceutical for the treatment of small hepatocellular carcinoma (HCC). 18,19 However, DW-166HC is sensitive to degradation induced by radiation and its use immediately after synthesis is highly required.…”