The superior predictive value of  166 Ho-scout compared with  99m Tc-macroaggregated albumin prior to  166 Ho-microspheres radioembolization in patients with liver metastases

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Abstract

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.

Related collections

Most cited references 16

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99mTc-macroaggregated albumin poorly predicts the intrahepatic distribution of 90Y resin microspheres in hepatic radioembolization.

Klaas van Gisbergen, Mattijs Elschot, J F M Nijsen … (2013)

In hepatic (90)Y radioembolization, pretreatment (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) nuclear imaging is used for lung shunt analysis, evaluation of extrahepatic deposition, and sometimes for treatment planning, using a partition model. A high level of agreement between pretreatment (99m)Tc-MAA distribution and final (90)Y-microsphere distribution is assumed. The aim of this study was to investigate the value of pretreatment (99m)Tc-MAA SPECT to predict intrahepatic posttreatment (90)Y-microsphere distribution. Volumes of interest (VOIs) were delineated on pretreatment contrast-enhanced CT or MR images according to Couinaud liver segmentation. All VOIs were registered to the (99m)Tc-MAA SPECT and (90)Y SPECT images. The (99m)Tc-MAA SPECT and (90)Y SPECT activity counts were normalized to the total administered activity of (90)Y. For each VOI, this practice resulted in a predictive amount of (90)Y (MBq/cm(3)) based on (99m)Tc-MAA SPECT in comparison with an actual amount of (90)Y based on (90)Y SPECT. Bland-Altman analysis was used to investigate the agreement of the activity distribution between (99m)Tc-MAA SPECT and (90)Y SPECT. A total of 39 procedures (225 VOIs) in 31 patients were included for analysis. The overall mean difference between pretreatment and posttreatment distribution of activity concentration for all segments was -0.022 MBq/cm(3) with 95% limits of agreement of -0.581 to 0.537 MBq/cm(3) (-28.9 to 26.7 Gy absorbed dose). A difference of >10%, >20%, and >30% of the mean activity per milliliter was found in, respectively, 153 (68%), 97 (43%), and 72 (32%) of the 225 segments. In every (99m)Tc-MAA procedure, at least 1 segment showed an under- or overestimation of >10%. The position of the catheter tip during administrations, as well as the tumor load of the liver segments, significantly influenced the disagreement. In current clinical practice, (99m)Tc-MAA distribution does not accurately predict final (90)Y activity distribution. Awareness of the importance of catheter positioning and adherence to specific recommendations may lead to optimization of individualized treatment planning based on pretreatment imaging.

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Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study.

Maarten Smits, Johannes Nijsen, Maurice van den Bosch … (2012)

The efficacy of radioembolisation for the treatment of liver tumours depends on the selective distribution of radioactive microspheres to tumorous tissue. The distribution of holmium-166 ((166)Ho) poly(L-lactic acid) microspheres can be visualised in vivo by both single-photon-emission CT (SPECT) and MRI. In this phase 1 clinical trial, we aimed to assess the safety and the maximum tolerated radiation dose (MTRD) of (166)Ho-radioembolisation in patients with liver metastases. Between Nov 30, 2009, and Sept 19, 2011, patients with unresectable, chemorefractory liver metastases were enrolled in the Holmium Embolization Particles for Arterial Radiotherapy (HEPAR) trial. Patients were treated with intra-arterial (166)Ho-radioembolisation in cohorts of three patients, with escalating aimed whole-liver absorbed doses of 20, 40, 60, and 80 Gy. Cohorts were extended to a maximum of six patients if dose-limiting toxicity occurred. Patients were assigned a dose in the order of study entry, with dose escalation until dose-limiting toxicity was encountered in at least two patients of a dose cohort. Clinical or laboratory toxicities were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. The primary endpoint was the MTRD. Analyses were per protocol. This study is registered with ClinicalTrials.gov, number NCT01031784. 15 patients underwent (166)Ho-radioembolisation at doses of 20 Gy (n=6), 40 Gy (n=3), 60 Gy (n=3), and 80 Gy (n=3). Mean estimated whole-liver absorbed doses were 18 Gy (SD 2) for the 20 Gy cohort, 35 Gy (SD 1) for the 40 Gy cohort, 58 Gy (SD 3) for the 60 Gy cohort, and 73 Gy (SD 4) for the 80 Gy cohort. The 20 Gy cohort was extended to six patients because of the occurrence of dose-limiting toxicity in one patient (pulmonary embolism). In the 80 Gy cohort, dose-limiting toxicity occurred in two patients: grade 4 thrombocytopenia, grade 3 leucopenia, and grade 3 hypoalbuminaemia in one patient, and grade 3 abdominal pain in another patient. The MTRD was identified as 60 Gy. The most frequently encountered laboratory toxicities (including grade 1) were lymphocytopenia, hypoalbuminaemia, raised alkaline phosphatase, raised aspartate aminotransferase, and raised gamma-glutamyltransferase, which were all noted in 12 of 15 patients. Stable disease or partial response regarding target lesions was achieved in 14 of 15 patients (93%, 95% CI 70-99) at 6 weeks and nine of 14 patients (64%, 95% CI 39-84) at 12 weeks after radioembolisation. Compared with baseline, the average global health status and quality of life scale score at 6 weeks after treatment had decreased by 13 points (p=0·053) and by 14 points at 12 weeks (p=0·048). In all patients, technetium-99m ((99m)Tc)-macro-aggregated albumin SPECT, (166)Ho scout dose SPECT, and (166)Ho treatment dose SPECT showed similar patterns of the presence or absence of extrahepatic deposition of activity. (166)Ho-radioembolisation is feasible and safe for the treatment of patients with unresectable and chemorefractory liver metastases and enables image-guided treatment. Clinical (166)Ho-radioembolisation should be done with an aimed whole-liver absorbed dose of 60 Gy. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Author and article information

Contributors

Marnix G. E. H. Lam: m.lam@umcutrecht.nl

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur. J. Nucl. Med. Mol. Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 9 August 2019

Publication date PMC-release: 9 August 2019

Publication date (Print): 2020

Volume: 47

Issue: 4

Pages: 798-806

Affiliations

GRID grid.7692.a, ISNI 0000000090126352, Department of Radiology and Nuclear Medicine, , University Medical Center Utrecht, ; Heidelberglaan 100, 3584 CX Utrecht, The Netherlands

Author information

Maarten L. J. Smits http://orcid.org/0000-0003-4735-655X

Article

Publisher ID: 4460

DOI: 10.1007/s00259-019-04460-y

PMC ID: 7075844

PubMed ID: 31399801

SO-VID: 10830d6e-8f8f-43ab-8803-0e288ad3ef9d

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 6 May 2019

Date accepted : 23 July 2019

Funding

Funded by: University Medical Center Utrecht

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: technetium-99m-maa,holmium-166 microspheres,radioembolization,sirt,dosimetry

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: technetium-99m-maa, holmium-166 microspheres, radioembolization, sirt, dosimetry