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      PET/CT-Based Dosimetry in 90Y-Microsphere Selective Internal Radiation Therapy: Single Cohort Comparison With Pretreatment Planning on 99mTc-MAA Imaging and Correlation With Treatment Efficacy

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      , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD
      Medicine
      Wolters Kluwer Health

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          Abstract

          90Y PET/CT can be acquired after 90Y-microsphere selective radiation internal therapy (SIRT) to describe radioactivity distribution. We performed dosimetry using 90Y-microsphere PET/CT data to evaluate treatment efficacy and appropriateness of activity planning from 99mTc-MAA scan and SPECT/CT.

          Twenty-three patients with liver malignancy were included in the study. 99mTc-MAA was injected during planning angiography and whole body 99mTc-MAA scan and liver SPECT/CT were acquired. After SIRT using 90Y-resin microsphere, 90Y-microsphere PET/CT was acquired. A partition model (PM) using 4 compartments (tumor, intarget normal liver, out-target normal liver, and lung) was adopted, and absorbed dose to each compartment was calculated based on measurements from 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT, respectively, to be compared with each other. Progression-free survival (PFS) was evaluated in terms of tumor absorbed doses calculated by 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT results.

          Lung shunt fraction was overestimated on 99mTc-MAA scan compared with 90Y-microsphere PET/CT (0.060 ± 0.037 vs. 0.018 ± 0.026, P < 0.01). Tumor absorbed dose exhibited a close correlation between the results from 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT ( r = 0.64, P < 0.01), although the result from 99mTc-MAA SPECT/CT was significantly lower than that from 90Y-microsphere PET/CT (135.4 ± 64.2 Gy vs. 185.0 ± 87.8 Gy, P < 0.01). Absorbed dose to in-target normal liver was overestimated on 99mTc-MAA SPECT/CT compared with PET/CT (62.6 ± 38.2 Gy vs. 45.2 ± 32.0 Gy, P = 0.02). Absorbed dose to out-target normal liver did not differ between 99mTc-MAA SPECT/CT and 90Y-microsphere PET/CT ( P = 0.49). Patients with tumor absorbed dose >200 Gy on 90Y-microsphere PET/CT had longer PFS than those with tumor absorbed dose ≤200 Gy (286 ± 56 days vs. 92 ± 20 days, P = 0.046). Tumor absorbed dose calculated by 99mTc-MAA SPECT/CT was not a significant predictor for PFS.

          Activity planning based on 99mTc-MAA scan and SPECT/CT can be effectively used as a conservative method. Post-SIRT dosimetry based on 90Y-microsphere PET/CT is an effective method to predict treatment efficacy.

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          Most cited references35

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          Feasibility of 90Y TOF PET-based dosimetry in liver metastasis therapy using SIR-Spheres.

          (90)Y-labelled compounds used in targeted radiotherapy are usually imaged with SPECT by recording the bremsstrahlung X-rays of the beta decay. The continuous shape of the X-ray spectrum induces the presence of a significant fraction of scatter rays in the acquisition energy window, reducing the accuracy of biodistribution and of dosimetry assessments. The aim of this paper is to use instead the low branch of e(-) e(+) pair production in the (90)Y decay. After administration of (90)Y-labelled SIR-Spheres by catheterization of both liver lobes, the activity distribution is obtained by (90)Y time-of-flight (TOF) PET imaging. The activity distribution is convolved with a dose irradiation kernel in order to derive the regional dosimetry distribution. Evaluation on an anatomical phantom showed that the method provided an accurate dosimetry assessment. Preliminary results on a patient demonstrated a high-resolution absorbed dose distribution with a clear correlation with tumour response. This supports the implementation of (90)Y PET in selective internal radiation therapy of the liver.
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            Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours.

            A uniform distribution of yttrium-90 (90Y) microspheres throughout the entire liver has always been assumed for dose calculation in treating hepatic tumours. A simple mathematical model was formulated which allows estimation of the activities of a therapeutic dose of 90Y microspheres partitioned between the lungs, the tumour and the normal liver, and hence the radiation doses to them. The doses to the tumour and normal liver were verified by intra-operative direct beta-probing. The percentage of activity shunted to the lung and the tumour-to-normal tissue ratio (T/N) were obtained from gamma scintigraphy using technetium-99m-labelled macroaggregated albumin (MAA) which simulates the 90Y microspheres used in subsequent treatment. The intrahepatic activity was partitioned between the tumour and the normal liver based on the T/N and their masses determined from computerized tomography slices. The corresponding radiation doses were computed using the MIRD formula. The estimated radiation doses were correlated with the doses directly measured using a calibrated beta-probe at laparotomy by linear regression. The radiation doses to the tumour and the normal liver, estimated using the partition model, were close to that measured directly with coefficients of correlation for linear regression: 0.862 for the tumours and 0.804 for the normal liver compartment (P<0.001). The partition model permits a distinction between the radiation doses received by the tumour and the normal liver to be made and the doses thus estimated are close to the actual doses received. The optimal doses to the tumour and normal liver and hence the required quantity of 90Y microspheres to be administered can be easily predetermined.
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              Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients.

              The use of 90Y-microspheres to treat unresectable liver metastases originating from a variety of neuroendocrine tumors was reviewed. This is a retrospective review from 10 institutions of patients given 90Y-microsphere therapy for neuroendocrine hepatic metastases. Physical, radiographic, biochemical, and clinical factors associated with treatment and response were examined. All patients were followed with laboratory and imaging studies at regular intervals until death, or censured whether other therapy was given after brachytherapy. Toxicities (acute and late) were recorded, and survival of the group determined. A total of 148 patients were treated with 185 separate procedures. The median age was 58 years (26-95 years) at treatment with median performance status of Eastern Cooperative Oncology Group (0). The median activity delivered was 1.14 GBq (0.33-3.30 GBq) with a median of 99% of the planned activity able to be given (38.1%-147.4%). There were no acute or delayed toxicity of Common Terminology Criteria for Adverse Events v3.0 grade 3 in 67% of patients, with fatigue (6.5%) the most common side effect. Imaging response was stable in 22.7%, partial response in 60.5%, complete in 2.7% and progressive disease in 4.9%. No radiation liver failure occurred. The median survival is 70 months. Radioembolization with 90Y-microspheres to the whole liver, or lobe with single or multiple fractions are safe and produce high response rates, even with extensive tumor replacement of normal liver and/or heavy pretreatment. The acute and delayed toxicity was very low without a treatment related grade 4 acute event or radiation induced liver disease in this modest-sized cohort. The significant objective response suggests that further investigation of this approach is warranted.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                June 2015
                12 June 2015
                : 94
                : 23
                : e945
                Affiliations
                From the Department of Nuclear Medicine, Seoul National University Hospital (YSS, JCP, GJC, J-KC, DSL, KWK); Department of Nuclear Medicine, Seoul National University Bundang Hospital (YSS); and Department of Radiology, Seoul National University Hospital, Seoul, Korea (H-CK, JWC)
                Author notes
                Correspondence: Jin Chul Paeng, Department of Nuclear Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. E-mail: paengjc@ 123456snu.ac.kr
                Hyo-Cheol Kim, Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. E-mail: angiointervention@ 123456gmail.com
                Article
                00945
                10.1097/MD.0000000000000945
                4616469
                26061323
                42f68cc8-d3ff-4668-97bc-a597fe8ae1e9
                Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 20 April 2015
                : 5 May 2015
                : 6 May 2015
                Categories
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                Research Article
                Observational Study
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