Radioembolization of Hepatocellular Carcinoma with Built-In Dosimetry: First <i>in vivo</i> 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 ⁹⁰Y (⁹⁰Y-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 ¹⁸⁸Re-labeled MS (¹⁸⁸Re-MS) as a new and easily imageable TARE agent. <b>Methods:</b> MS made of poly(<i>L</i>-lactic acid) were produced in a flow focusing microchip. The MS were labeled with ¹⁸⁸Re 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 ¹⁸⁸Re-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. <b>Results:</b> The spherical ¹⁸⁸Re-MS had a diameter of 41.8 ± 6.0 µm (<i>CV</i> = 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. ¹⁸⁸Re-MS accumulated in the liver with no deposition in the lungs. ¹⁸⁸Re decays to stable ¹⁸⁸Os by emission of β^¯ particles with similar energy to those emitted by ⁹⁰Y 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. <b>Conclusions:</b>¹⁸⁸Re-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 ¹⁸⁸Re-MS in a large-scale, long-term preclinical study as well as the evaluation of the clinical outcomes of using ¹⁸⁸Re-MS with different sizes, from 20 to 50 µm.