Background: Intra-arterial radioembolization with yttrium-90 microspheres ( ⁹⁰Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( ¹⁶⁶Ho-PLLA-MS) have been developed as a possible alternative to ⁹⁰Y-RE. Next to high-energy beta-radiation, ¹⁶⁶Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of ¹⁶⁶Ho-PLLA-MS radioembolization ( ¹⁶⁶Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of ¹⁶⁶Ho-RE in patients with liver metastases. Methods: The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( ^99mTc-MAA) dose, a low radioactive safety dose of 60-mg ¹⁶⁶Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of ¹⁶⁶Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the ¹⁶⁶Ho-PLLA-MS safety dose and the ^99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution. Discussion: This will be the first clinical study on ¹⁶⁶Ho-RE. Based on preclinical studies, it is expected that ¹⁶⁶Ho-RE has a safety and toxicity profile comparable to that of ⁹⁰Y-RE. The biochemical and radionuclide characteristics of ¹⁶⁶Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure. Trial registration: ClinicalTrials.gov NCT01031784

Purpose As an alternative to technetium-99m-macroaggregated albumin (^99mTc-MAA), a scout dose of holmium-166 (¹⁶⁶Ho) microspheres can be used prior to ¹⁶⁶Ho-radioembolization. The use of identical particles for pre-treatment and treatment procedures may improve the predictive value of pre-treatment analysis of distribution. The aim of this study was to analyze the agreement between ¹⁶⁶Ho-scout and ¹⁶⁶Ho-therapeutic dose in comparison with the agreement between ^99mTc-MAA and ¹⁶⁶Ho-therapeutic dose. Methods Two separate scout dose procedures were performed (^99mTc-MAA and ¹⁶⁶Ho-scout) before treatment in 53 patients. First, qualitative assessment was performed by two blinded nuclear medicine physicians who visually rated the agreement between the ^99mTc-MAA, ¹⁶⁶Ho-scout, and ¹⁶⁶Ho-therapeutic dose SPECT-scans (i.e., all performed in the same patient) on a 5-point scale. Second, agreement was measured quantitatively by delineating lesions and normal liver on FDG-PET/CT. These volumes of interest (VOIs) were co-registered to the SPECT/CT images. The predicted absorbed doses (based on ^99mTc-MAA and ¹⁶⁶Ho-scout) were compared with the actual absorbed dose on post-treatment SPECT. Results A total of 23 procedures (71 lesions, 22 patients) were included for analysis. In the qualitative analysis, ¹⁶⁶Ho-scout was superior with a median score of 4 vs. 2.5 for ^99mTc-MAA (p < 0.001). The quantitative analysis showed significantly narrower 95%-limits of agreement for ¹⁶⁶Ho-scout in comparison with ^99mTc-MAA when evaluating lesion absorbed dose (− 90.3 and 105.3 Gy vs. − 164.1 and 197.0 Gy, respectively). Evaluation of normal liver absorbed dose did not show difference in agreement between both scout doses and ¹⁶⁶Ho-therapeutic dose (− 2.9 and 5.5 Gy vs − 3.6 and 4.1 Gy for ^99mTc-MAA and ¹⁶⁶Ho-scout, respectively). Conclusions In this study, ¹⁶⁶Ho-scout was shown to have a superior predictive value for intrahepatic distribution in comparison with ^99mTc-MAA.

Introduction Radioembolisation of liver tumours demands many choices from the physician regarding planning of treatment and subsequent follow-up. Methods An online questionnaire was distributed amongst all members of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) to investigate the current state of radioembolisation practice. Results The survey was completed by 60 centres. The increasing number of radioembolisation procedures may reflect that radioembolisation is increasingly recognised as a valuable treatment option in European cancer guidelines. Imaging modalities play an important role in decision making. Furthermore, there seems to be a trend towards less coil-embolisation of non-target vessels. In addition, type of microsphere, model for dose calculation, complications and future developments are evaluated in this article. Conclusions This survey provides insight into the current state of radioembolisation practice across Europe.

Purpose: We present a technique that combines Hepatic Arteriography with C-arm CT-Guided Ablation (HepACAGA) to improve tumor visualization, navigation and margin confirmation for percutaneous ablation of liver tumors. Materials and Methods: All consecutive patients scheduled for HepACAGA between April 20th, 2021, and November 2nd, 2021, were included in this retrospective, cohort study. HepACAGA was performed in an angiography-suite under general anesthesia. The hepatic artery was catheterized for selective contrast injection. C-arm CT and guidance software were then used to visualize the tumor and the microwave antenna was inserted during apnea. Pre- and post-ablation C-arm CTs were performed and ablation margins assessed. Technical success, antenna placement deviation, number of repositions, tumor recurrence, and safety were evaluated. Technical success was defined as a tumor that was ablated according to the HepACAGA technique. Results: A total of 21 patients (28 tumors) were included. The main tumor type was colorectal cancer liver metastases (11/21, 52%), followed by hepatocellular carcinoma (7/21, 33%), neuroendocrine tumor metastases (1/21, 5%), and other tumor types (2/21, 10%). The technical success rate was 93% (26/28 tumors) with two small hypovascular lesions unable to be identified. A single microwave antenna was used in all patients. The median antenna placement deviation was 1 mm (range 0–6 mm). At a median follow-up time of 16 months (range 5–22 months), there was no tumor recurrence in any patient. Safety analysis showed a complication rate of 5% grade 2 and 5% grade 3. Conclusion: HepACAGA was demonstrated to be a safe and effective percutaneous ablation technique, without any local tumor recurrence in this study. Graphic