Radioembolization of Hepatocellular Carcinoma with Built-In Dosimetry: First in vivo Results with Uniformly-Sized, Biodegradable Microspheres Labeled with ¹⁸⁸Re

Abstract

A common form of treatment for patients with hepatocellular carcinoma (HCC) is transarterial radioembolization (TARE) with non-degradable glass or resin microspheres (MS) labeled with 90 Y ( 90 Y-MS). To further simplify the dosimetry calculations in the clinical setting, to have more control over the particle size and to change the permanent embolization to a temporary one, we developed uniformly-sized, biodegradable 188 Re-labeled MS ( 188 Re-MS) as a new and easily imageable TARE agent. Methods: MS made of poly( L -lactic acid) were produced in a flow focusing microchip. The MS were labeled with 188 Re using a customized kit. An orthotopic HCC animal model was developed in male Sprague Dawley rats by injecting N1-S1 cells directly into the liver using ultrasound guidance. A suspension of 188 Re-MS was administered via hepatic intra-arterial catheterization 2 weeks post-inoculation of the N1-S1 cells. The rats were imaged by SPECT 1, 24, 48, and 72 h post-radioembolization. Results: The spherical 188 Re-MS had a diameter of 41.8 ± 6.0 µm ( CV = 14.5%). The site and the depth of the injection of N1-S1 cells were controlled by visualization of the liver in sonograms. Single 0.5 g tumors were grown in all rats. 188 Re-MS accumulated in the liver with no deposition in the lungs. 188 Re decays to stable 188 Os by emission of β ¯ particles with similar energy to those emitted by 90 Y while simultaneously emitting γ photons, which were imaged directly by single photon computed tomography (SPECT). Using Monte Carlo methods, the dose to the tumors was calculated to be 3-6 times larger than to the healthy liver tissue. Conclusions: 188 Re-MS have the potential to become the next generation of β ¯ -emitting MS for TARE. Future work revolves around the investigation of the therapeutic potential of 188 Re-MS in a large-scale, long-term preclinical study as well as the evaluation of the clinical outcomes of using 188 Re-MS with different sizes, from 20 to 50 µm.

Polydopamine-Coated Radiolabeled Microspheres for Combinatorial Radioembolization and Photothermal Cancer Therapy

“…Arterial cannulation of orthotopic HCC tumors in rats has been widely used for embolization studies. , The orthotopic HCC tumor model was constructed by injecting N1S1 cells into the rat liver. When the tumor volume reached around 200 mm 3 monitored by MRI, the rats were ready for the subsequent experiments.…”

Bench-to-bedside development of multifunctional flexible embolic agents

“…There are two types of commercially available 90 Y microspheres for treating hepatic neoplasms, namely 1) TheraSphere ® (BTG International, London, United Kingdom) and 2) Sir-Spheres ® (Sirtex Medical Europe, Bonn, G) [152,156]. All other radioactive microspheres are either investigational or not clinical, such as 166 Ho and 188 Rebased microspheres [157,158]. TheraSphere ® is composed of nonbiodegradable glass, in which 90 Y radioisotope act as an integral constituent of the glass matrix.…”

Transarterial Radioembolization: Overview of Radioembolic Devices

“…7 More recently, rhenium-188 (Re-188)-labeled lipiodol has been evaluated, with preclinical studies showing safety and efficacy. 8…”