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

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 ¹⁶⁶Ho-SD in a clinical setting.

Key points: • A holmium-166 scout dose is safe in a clinical setting. • Holmium-166 scout dose is a safe alternative for ^99m Tc-MAA for radioembolisation work-up. • Holmium-166 scout dose potentially has several benefits over ^99m Tc-MAA for radioembolisation work-up.

Keywords: Embolisation, therapeutic; Holmium; Radioembolisation; SIRT; Technetium Tc-99m Aggregated Albumin.

Fig. 1

A 63-year-old female with an intrahepatic cholangiocarcinoma. (a) Digital subtraction angiography (DSA) image with injection position in right hepatic artery. (b) ¹⁶⁶Ho scout dose SPECT/CT with duodenal extrahepatic deposition (arrow). On DSA, posterior superior pancreatico-duodenal artery was the culprit vessel (arrow), which in 15% of cases originates from the common hepatic artery or main hepatic artery [13]. However, it can also arise from the right hepatic artery [14], as illustrated here

Fig. 2

An 80-year-old female with colorectal cancer liver metastases was initially treated with a resection of her sigmoid carcinoma and simultaneous right hemihepatectomy. (a) Digital subtraction angiography (DSA) with injection position during ¹⁶⁶Ho scout dose pre-treatment angiography. (b) SPECT/CT after administration of ¹⁶⁶Ho scout dose with large extrahepatic deposition in lesser curvature of the stomach (arrows). (c) DSA showing the right gastric artery arising from the right hepatic artery as culprit vessel (arrows)

Fig. 3

A 63-year-old male with colorectal cancer liver metastases. (a) Digital subtraction angiogram (DSA) of injection position of ¹⁶⁶Ho scout dose procedure. (b) ¹⁶⁶Ho scout dose SPECT/CT with extrahepatic deposition in duodenum (star). (c) DSA of injection position of ¹⁶⁶Ho therapy. Note the difference in positioning of microcatheter (arrows). During ¹⁶⁶Ho scout dose procedure the microcatheter pointed downwards, instead of horizontally (arrows). On the same DSA of ¹⁶⁶Ho scout dose procedure the culprit vessel, supraduodenal artery, can be identified (arrowhead)

Fig. 4

A 62-year-old female with liver metastases of a pancreatic adenocarcinoma. (a) SPECT/CT after administration of ¹⁶⁶Ho scout dose. Extrahepatic deposition in the duodenum (arrow). (b) Digital subtraction angiography shows flow redistribution in intrahepatic collateral (arrows), directly following coil embolization of gastroduodenal artery. Development of new hepatico-enteric collaterals after previous coil embolization has been described before [15]

Fig. 5

A 56-year-old male with a primary rectal neuroendocrine tumour, liver and bone metastases. (a) Digital subtraction angiography of ¹⁶⁶Ho scout dose procedure. (b) Corresponding ¹⁶⁶Ho scout dose SPECT/CT. (c) Corresponding cone beam CT. All images show extrahepatic deposition and contrast blush in gastric fundus (arrows). After coiling of accessory left gastric artery, extrahepatic deposition on SPECT/CT and contrast blush on cone beam CT disappeared (images not shown). Accessory left gastric artery originated distally from left hepatic artery, running through the ligamentum venosum towards the gastric fundus [16]

Fig. 6

A 60-year-old male with colorectal liver metastases. (a) Planar ¹⁶⁶Ho image of scout dose, depicting a faint extrahepatic deposition in falciform ligament. (b) Post-treatment planar ¹⁶⁶Ho image, depicting similar extrahepatic deposition in falciform ligament (SPECT/CT images not shown)

Fig. 7

(a) Graph featuring results of threshold-based volume estimation of six ¹⁶⁶Ho-filled spheres in NEMA NU-2 Image Quality phantom (0.5–26.5 ml). (b) Threshold-estimated absorbed doses relative to their true value in phantom spheres, using 30% threshold and known ¹⁶⁶Ho acidic solution concentration. Underestimation of affected tissue volume in vivo will occur, subsequently leading to overestimation of absorbed tissue dose (up to four times in sphere 3 of 2.6 ml). A slight underestimation of the absorbed dose will only occur in small-volume extrahepatic depositions (<1 ml)