Learning Objectives: On successful completion of this activity, participants should be able to (1) describe the status of the current literature regarding new indications for radioembolization; (2) describe standard hepatic vascularization, identify common routes for extrahepatic depositions, and judge when "skeletization" of hepatic arteries could be unnecessary; and (3) appraise the different methods of activity calculation and recognize the strengths and pitfalls of pretreatment and posttreatment dosimetry.Financial Disclosure: Dr. Lam is a consultant/advisor for BTG International and a meeting participant/lecturer for SirTex Medical. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through July 2018.Radioembolization is an established treatment modality that has been subjected to many improvements over the last decade. Developments are occurring at a high pace, affecting patient selection and treatment. The aim of this review is therefore to provide an overview of current practice, with a focus on recent developments in the field of radioembolization. Several practical issues and recommendations in the application of radioembolization will be discussed, ranging from patient selection to treatment response and future applications.

Randomized controlled trials are investigating the benefit of hepatic radioembolization added to systemic therapy in the first-and second-line treatment of patients with colorectal liver metastases (CRLM). Remarkably, administered activity may still be suboptimal, because a dose-response relationship has not been defined. The purpose of this study was to characterize the relationship between tumor-absorbed dose and response after 90 Y radioembolization treatment for CRLM. Methods: Thirty patients with unresectable chemorefractory CRLM were treated with resin 90 Y-microspheres in a prospective phase II clinical trial. Tumor-absorbed dose was quantified on 90 Y PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG*) on 18 F-FDG PET, was measured at baseline and 1 mo after treatment. The relationship between tumor-absorbed dose and posttreatment metabolic activity was assessed per metastasis with a linear mixed-effects regression model. Results: Treated metastases (n 5 133) were identified. The mean tumorabsorbed dose was 51 ± 28 Gy (range, 7-174 Gy). A 50% reduction in TLG* was achieved in 46% of metastases and in 11 of 30 (37%) patients for the sum of metastases. The latter was associated with a prolonged median overall survival (11.6 vs. 6.6 mo, P 5 0.02). A strong and statistically significant dose-response relationship was found (P , 0.001). The dose effect depended on baseline TLG* (P , 0.01). The effective tumor-absorbed dose was conservatively estimated at a minimum of 40-60 Gy. Conclusion: A strong dose-response relationship exists for the treatment of CRLM with resin microsphere 90 Y radioembolization. Treatment efficacy is, however, still limited, because the currently used pretreatment activity calculation methods curb potentially achievable tumor-absorbed dose values. A more personalized approach to radioembolization is required before concluding on its clinical potential.

Radioembolization of liver malignancies with Ho-microspheres has been shown to be safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy ofHo radioembolization. In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. The primary outcome was a response by 2 target lesions on triphasic liver CT scans 3 mo after therapy, as assessed using RECIST, version 1.1. Secondary outcomes included overall tumor response, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI. Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27 (73%) of 37 patients, the target lesions showed complete response, partial response, or stable disease (disease control) at 3 mo (95% confidence interval [CI], 57%-85%). The median overall survival was 14.5 mo (95% CI, 8.6-22.8 mo). For colorectal cancer patients ( = 23), the median overall survival was 13.4 mo (95% CI, 8.2-15.7 mo). Grade 3 or 4 toxic events after treatment (according to the Common Terminology Criteria for Adverse Events, version 4.03) included abdominal pain (in 18% of patients), nausea (8%), ascites (3%), fatigue (3%), gastric stenosis (3%), hepatic failure (3%), liver abscesses (3%), paroxysmal atrial tachycardia (3%), thoracic pain (3%), upper gastrointestinal hemorrhage (3%), and vomiting (3%). On SPECT, Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3% ± 7.1% in the liver. Radioembolization with Ho-microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.