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

José Carlos De La Vega; Pedro Luis Esquinas; Cristina Rodríguez-Rodríguez; Mehrdad Bokharaei; Igor Moskalev; David Liu; Katayoun Saatchi; Urs O Häfeli

doi:10.7150/thno.29381

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

Theranostics. 2019 Jan 25;9(3):868-883. doi: 10.7150/thno.29381. eCollection 2019.

Authors

José Carlos De La Vega¹, Pedro Luis Esquinas², Cristina Rodríguez-Rodríguez^{1

3}, Mehrdad Bokharaei¹, Igor Moskalev⁴, David Liu⁵, Katayoun Saatchi¹, Urs O Häfeli¹

Affiliations

¹ Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC Canada.
² Department of Radiology, University of British Columbia, Vancouver, BC Canada.
³ Department of Physics and Astronomy, University of British Columbia, Vancouver, BC Canada.
⁴ The Vancouver Prostate Cancer Centre and Department of Urologic Sciences, University of British Columbia, Vancouver, BC Canada.
⁵ Department of Interventional Radiology, Vancouver General Hospital, Vancouver, BC Canada.

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. Methods: MS made of poly(L-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. Results: The spherical ¹⁸⁸Re-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. 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. Conclusions: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.

Keywords: 188Re; beta radiation therapy; liver cancer; microspheres; monosized; radioembolization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Hepatocellular / diagnosis
Carcinoma, Hepatocellular / therapy*
Disease Models, Animal
Drug Carriers*
Embolization, Therapeutic / methods*
Humans
In Vivo Dosimetry / methods
Liver Neoplasms / diagnosis
Liver Neoplasms / therapy
Microspheres*
Polyesters
Radioisotopes / administration & dosage*
Radiotherapy / methods*
Rats, Sprague-Dawley
Rhenium / administration & dosage*
Treatment Outcome

Substances

Drug Carriers
Polyesters
Radioisotopes
poly(lactide)
Rhenium

Grants and funding

CIHR/Canada