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. 2018 Mar;28(3):920-928.
doi: 10.1007/s00330-017-4998-2. Epub 2017 Aug 7.

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  2 , Rob van Rooij  2 , Rutger C G Bruijnen  2 , Maurice A A J van den Bosch  2 , Marnix G E H Lam  2
Affiliations

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

Arthur J A T Braat et al. Eur Radiol. 2018 Mar.

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.

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Conflict of interest statement

Guarantor

The scientific guarantor of this publication is Prof. Dr. M.G.E.H. Lam, nuclear medicine physician and head of the Nuclear Medicine department.

Conflict of interest

MGEHL has acted as a consultant for BTG, Sirtex, Mirada and Bayer Healthcare. The University Medical Centre Utrecht (UMC Utrecht) receives royalties from Quirem Medical, producer of 166Ho microspheres.

AJATB, JFP, RvR, RCGB and MAAJvdB declare no relationships with any companies whose products or services may be related to the subject matter of the article

Funding

Research projects mentioned in de manuscript received funding by the Dutch Cancer Society (KWF Kankerbestrijding), under grant UU2009-4346 and by the Technology Foundation STW under grant 6069.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in all the separate trials mentioned in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study overlap, subjects or cohorts have been previously reported. An earlier clinical phase 1 study investigating efficacy and toxicity of radioembolisation with 166Ho microspheres in 15 patients was reported. These 15 patients were analysed in this study as well; however, the emphasis in this study is on the 166Ho scout dose and not the actual treatment with 166Ho microspheres (Smits et al. Lancet Oncol 2012; 13(10):1025-34. doi: 10.1016/S1470-2045(12)70334-0)

Methodology

• prospective

• observational

• performed at one institution

Figures

Fig. 1
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
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
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
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
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
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
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)
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References

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