Holmium radioembolization of liver metastases

Liver metastases are a common disorder that can be caused by a variety of primary tumors throughout the body. Treatment of liver metastases can be challenging and often comes with a substantial morbidity and mortality. Holmium-166 (166Ho)microspheres have been developed as an alternative to the currently clinically used yttrium-90 microspheres for radioembolization of liver tumors. Besides the high-energy beta-radiation required for tumor destruction, 166Ho also emits low-energy gamma radiation, which can be used for quantitative gamma imaging (SPECT) and the paramagnetic property of holmium can be used for magnetic resonance imaging (MRI). This thesis presents the results of the first 166Ho-radioembolization treatments performed in human patients and relates these findings to studies on radioembolization with yttrium-90-microspheres. The thesis is subdivided in two parts: Part I: Response and Toxicity, and Part II: Imaging and Dosimetry. A phase 1 study was performed in 15 patients with unresectable liver metastases. Patients received escalating doses of 166Ho-radioembolization. The maximum tolerated radiation dose, toxicity, tumor response, survival, quality of life, and dosimetry with SPECT and MRI were evaluated. It was concluded that 166Ho-radioembolization can be safely performed in this patient category at an aimed-whole liver dose of 60 Gy. The characteristics of 166Ho allow for accurate dosimetry with SPECT and/or MRI. Future studies will need to establish the efficacy of 166Ho-radioembolization and further exploit the dosimetry options for personalized treatment