Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov;45(11):1634-1645.
doi: 10.1007/s00270-022-03187-y. Epub 2022 Jun 21.

Holmium-166 Radioembolization: Current Status and Future Prospective

Martina Stella  1 , Arthur J A T Braat  2 , Rob van Rooij  2 , Hugo W A M de Jong  2 , Marnix G E H Lam  2
Affiliations
Review

Holmium-166 Radioembolization: Current Status and Future Prospective

Martina Stella et al. Cardiovasc Intervent Radiol. 2022 Nov.

Abstract

Since its first suggestion as possible option for liver radioembolization treatment, the therapeutic isotope holmium-166 (166Ho) caught the experts' attention due to its imaging possibilities. Being not only a beta, but also a gamma emitter and a lanthanide, 166Ho can be imaged using single-photon emission computed tomography and magnetic resonance imaging, respectively. Another advantage of 166Ho is the possibility to perform the scout and treatment procedure with the same particle. This prospect paves the way to an individualized treatment procedure, gaining more control over dosimetry-based patient selection and treatment planning. In this review, an overview on 166Ho liver radioembolization will be presented. The current clinical workflow, together with the most relevant clinical findings and the future prospective will be provided.

Keywords: Dosimetry; Holmium-166; MRI; Radioembolization; SPECT/CT.

PubMed Disclaimer

Conflict of interest statement

MS is employed by the UMC Utrecht under a collaborative grant of the Dutch Research Council (NWO) between UMC Utrecht and Quirem Medical BV. RvR and HWAMdJ have acted as a consultant for BTG/Boston Scientific. AJATB has acted as consultant for BTG/Boston Scientific and Terumo. MGEHL has acted as a consultant for BTG/Boston Scientific and Terumo, and receives research support from BTG/Boston Scientific and Quirem Medical BV. The Department of Radiology and Nuclear Medicine of the UMC Utrecht receives royalties from Quirem Medical BV. No other potential conflicts of interest relevant to this article exist.

Figures

Fig. 1
Fig. 1
On the left, the steps of the clinical workflow for 166Ho liver radioembolization are depicted. On the right, images referring to an exemplary clinical case are reported. A 73 years old female patient diagnosed with hepatocellular carcinoma was referred for 166Ho radioembolization. Among others, she presented a lesion in segment 6 with a maximum diameter of 71 mm, as it is possible to see from the baseline MRI reported in panel A. During the workup angiography (panel B), coil embolization of the segment 4 artery was performed to obtain intrahepatic redistribution. Consequently, activity initially planned for segment 4 was added to the activity injected in the right hepatic artery, for a total of 122 MBq. In the SPECT/CT acquired after the scout procedure and displayed in panel C, it is possible to see a clear 166Ho uptake in the segment 6, where the tumor lesion was located. No extrahepatic deposition was reported, confirming a successful scout procedure. After having planned the treatment aiming at 60 Gy average absorbed dose to the whole liver (panel D), 4116 166Ho MBq was injected into the right hepatic artery (panel E). 3 days after the treatment, a SPECT/CT was acquired to visually confirm the good targeting of tumor in segment 6 (panel F). Post-treatment dosimetry revealed a good targeting of the tumor, which received a mean dose of 137 Gy, and a safe uptake by the healthy liver, which had a mean absorbed dose of 36 Gy. The MRI acquired 3 months after the treatment (panel G) showed a decrease in lesion size of segment 6 from 71 to 42 mm and complete disappearance of contrast enhancement (complete response according to mRECIST)
Fig. 2
Fig. 2
85 year old male diagnosed with hepatocellular carcinoma (HCC). At presentation, contrast enhanced T1 MRI (A), a solitary hypervascular lesion in segment 5, 6 and 8 with a maximum diameter of 8.1 cm was seen. At tumor board, the patient was considered for first-line SIRT. The 166Ho scout procedure consisted of a single injection of 233 MBq of 166Ho microspheres in the right hepatic artery (B) and subsequent SPECT/CT imaging showed no lung shunt, no extrahepatic deposition of activity elsewhere and visually good tumor targeting. The patient proceeded with 166Ho treatment in the afternoon (on the same day), in which 4.3 GBq of 166Ho microspheres were administered in the right hepatic artery (B). 3 months after treatment, follow-up contrast enhanced T1 MRI (C), showed a good response reducing its size from 8.1 cm to 5.8 cm and complete response according to mRECIST. Post-treatment SPECT/CT (D) 3 days after treatment confirmed the planned high accumulation of particles in the lesion, without extrahepatic deposition of activity (and no lung shunt). At this moment, more than 3 years after treatment, the patient has no signs of recurrent disease on imaging
Fig. 3
Fig. 3
64 year old male diagnosed with intrahepatic metastatic cholangiocarcinoma (ICC), with distinct lesions in segment 8, 4 and a minor lesion on the edge of segment 3/4B (A and B). At tumor board, he was considered to be eligible for radioembolization treatment with 166Ho microspheres, which he received after an uneventful 166Ho scout procedure. On the day of treatment a superselective injection of 1.6 GBq (radiation segmentectomy) in segment 8 (C) and segmental injection of 0.8 GBq in segment 4 (D) was executed. Post-treatment SPECT/CT showed a good accumulation of particles around the tumor in segment 8 (E) and segment 4 (F). Contrast enhanced CT (G + H) and 18FDG-PET (not shown) acquired 2 months after treatment showed a near complete regression of the segment 8 lesion and partial response of the segment 4 lesion. Recent follow-up treatment (not shown) consisted of additional 166Ho radioembolization of segment 4 and superselective in segment 3. Segment 8 lesion is still in (near) complete remission
Fig. 4
Fig. 4
Summary of the clinical studies on 166Ho radioembolization completed between 2009 and 2021
Fig. 5
Fig. 5
Dual isotope workflow. Firstly, 166Ho microspheres are injected (during either the scout or the treatment procedure), lodging primarily in the tumorous tissues. Additionally, 99mTc-stannous phytate is injected on the SPECT table, accumulating in the Kupffer cells representing the healthy liver tissue. Then a conventional SPECT/CT is acquired that simultaneously acquires two isotopes (166Ho and 99mTc), after which the images are reconstructed correcting the reciprocal scatter caused by the concomitant presence of the two isotopes. These reconstructions are intrinsically registered and thus can be used to automatically define treated tumors and healthy liver avoiding segmentation and registration of a separately acquired CT, which is time-consuming and prone to error
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Riemenschneider T, Ruf C, Kratzsch HC, Ziegler M, Späth G. Arterial, portal or combined arterio-portal regional chemotherapy in experimental liver tumours? J Cancer Res Clin Oncol. 1992;118(8):597–600. doi: 10.1007/BF01211803. - DOI - PubMed
    1. Mumper RJ, Ryo UY, Jay M. Acid microspheres: a potential agent for the internal radiation therapy of hepatic tumors. J Nucl Med. 1991;32(11):2139–2143. - PubMed
    1. Turner JH, et al. 166Ho-Microsphere liver radiotherapy: a preclinical SPECT dosimetry study in the pig. Nucl Med Commun. 1994;15(7):545–553. doi: 10.1097/00006231-199407000-00009. - DOI - PubMed
    1. Nijsen F, et al. Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study. Eur J Nucl Med. 2001;28(6):743–749. doi: 10.1007/s002590100518. - DOI - PubMed
    1. Smits ML, et al. Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial. J Exp Clin Cancer Res. 2010;29(1):70. doi: 10.1186/1756-9966-29-70. - DOI - PMC - PubMed

MeSH terms

Grants and funding