Safety analysis of holmium-166 microsphere scout dose imaging during radioembolisation work-up: A cohort study

Eur Radiol DOI 10.1007/s00330-017-4998-2 INTERVENTIONAL Safety analysis of holmium-166 microsphere scout dose imaging during radioembolisation work-up: A cohort study Arthur J. A. T. Braat 1 & Jip F. Prince 1 & Rob van Rooij 1 & Rutger C. G. Bruijnen 1 & Maurice A. A. J. van den Bosch 1 & Marnix G. E. H. Lam 1 Received: 31 January 2017 / Revised: 21 May 2017 / Accepted: 18 July 2017 # The Author(s) 2017. This article is an open access publication Abstract Objective Radioembolisation is generally preceded by a scout dose of technetium-99m-macroaggregated albumin to estimate extrahepatic shunting of activity. Holmium-166 microspheres can be used as a scout dose (±250 MBq) and as a therapeutic dose. The general toxicity of a holmium-166 scout dose (166Ho-SD) and safety concerns of an accidental extrahepatic deposition of 166Ho-SD were investigated. Methods All patients who received a 166Ho-SD in our institute were reviewed for general toxicity and extrahepatic depositions. The absorbed dose in extrahepatic tissue was calculated on SPECT/CT and correlated to clinical toxicities. Results In total, 82 patients were included. No relevant clinical toxicity occurred. Six patients had an extrahepatic deposition of 166Ho-SD (median administered activity 270 MBq). The extrahepatic depositions (median activity 3.7 MBq) were located in the duodenum (3x), gastric fundus, falciform ligament and the lesser curvature of the stomach, and were deposited in a median volume of 15.3 ml, which resulted in an estimated median absorbed dose of 3.6 Gy (range 0.3– 13.8 Gy). No adverse events related to the extrahepatic deposition of the 166Ho-SD occurred after a median follow-up of 4 months (range 1–12 months). Conclusion These results support the safety of 250 MBq 166 Ho-SD in a clinical setting. * Arthur J. A. T. Braat 1 Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, Huispostnummer E01.132, 3584 CX Utrecht, The Netherlands Key Points • A holmium-166 scout dose is safe in a clinical setting. • Holmium-166 scout dose is a safe alternative for 99mTc-MAA for radioembolisation work-up. • Holmium-166 scout dose potentially has several benefits over 99mTc-MAA for radioembolisation work-up. Keywords Radioembolisation . SIRT . Holmium . Embolisation, therapeutic . Technetium Tc-99m Aggregated Albumin Introduction Before yttrium-90 (90Y) radioembolisation (RE) is performed, a scout dose is used to predict intra- and extrahepatic distribution of activity and check for potential contraindications (i.e. excessive lung shunt and extrahepatic depositions). Technetium-99m macro aggregated albumin (99mTc-MAA) is commonly used; however, its predictive value has been discussed in the literature [1, 2]. In patients treated with holmium-166 ( 166Ho) microspheres a scout dose using 250 MBq 166Ho is used as an alternative, which is superior in calculating the lung shunt fraction compared to 99mTcMAA [1]. This may be due to the fact that identical 166Ho microspheres are used for the scout dose procedure and the RE treatment. The beta- and gamma-emitting properties of 166Ho (respectively Eβmax = 1.85 MeV and Eγ = 81 keV) may theoretically raise concerns about the safety of using 166Ho microspheres as a scout dose. An earlier study concluded that 166Ho microspheres can safely replace 99mTc-MAA in the majority of cases [3]. However, these data were based on 99mTc-MAA data of extrahepatic depositions, theoretically translated to 166 Ho microspheres; if these extrahepatic 99m Tc-MAA Eur Radiol depositions had been 166Ho microspheres, only 5.9% of patients would have excessive absorbed doses in extrahepatic tissues [3]. This toxicity assessment was performed because of a lack of events after 166Ho microsphere scout dose procedures. Since then, a 166Ho microsphere scout dose (166Ho scout dose) has been used in several clinical trials. Several events in the use of an extrahepatic 166Ho scout dose were observed that warrant a re-evaluation of the previous theoretically based safety assumptions. To assess the safety of the 166Ho scout dose in clinical practice, the general toxicity of a 166Ho scout dose was studied. Additionally, the absorbed dose in extrahepatic tissue in all patients with an extrahepatic 166Ho scout dose deposition was calculated and clinical record forms for potential complications due to these extrahepatic depositions were reviewed. Methods and materials Patient population All patients who had been treated with 166Ho microspheres since the start of its clinical use were included, i.e. from November 2009 till January 2016. All patients included in this study participated in a prospective trial with 166Ho microspheres (Table 1 [4–7]) and written informed consent was obtained for all patients at study inclusion. All data were gathered prospectively and all studies were approved by the institution’s Ethics Committee prior to patient inclusion. Results of 15 patients treated with 166Ho radioembolisation in the HEPAR trial have been published previously [4]. This earlier article dealt with development of the 166Ho microspheres as a therapeutic agent, whereas this current study provides additional information solely on the toxicity of the 166 Ho scout dose of those patients. The scout dose with 166 Ho microspheres was aimed at 250 MBq in all study protocols and administered intra-arterially. The 250 MBq was divided amongst the injection positions according to the targeted liver volume. All patients received the scout dose administration in the morning prior to the therapeutic 166Ho dose administration in the afternoon on the same day. In patients with an extrahepatic deposition, additional volume, activity and dose quantification on imaging studies were performed and discussed separately (details in the next sections). Clinical record forms were evaluated for any adverse events during or after the 166Ho scout dose procedure and prior to the radioembolisation treatment with 166Ho microspheres. They were scored according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Angiography procedures were performed by experienced interventional radiologists (>3 years’ experience) and SPECT/CT readings by experienced nuclear medicine physicians (>3 years’ experience). Imaging and reconstruction Our phantom and all patients were scanned on a Symbia T16 SPECT/CT scanner (Siemens Healthcare, Erlangen, Germany) within 1 h of the injection of the 166Ho scout dose. Similar to 99mTc-MAA, lung shunt fraction (LSF) was determined by drawing regions-of-interest (ROIs) of the lungs and the liver on anterior and posterior planar imaging of the thorax and abdomen. By calculating the fraction of the total activity using the geometric mean, resulting in the following equation: qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi  ffi lungsanterior *lungsposterior LS F ¼ qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi  ffi qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi (...truncated)