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

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

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