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      Quantitative Comparison of PET and Bremsstrahlung SPECT for Imaging the In Vivo Yttrium-90 Microsphere Distribution after Liver Radioembolization

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          Abstract

          Background

          After yttrium-90 ( 90Y) microsphere radioembolization (RE), evaluation of extrahepatic activity and liver dosimetry is typically performed on 90Y Bremsstrahlung SPECT images. Since these images demonstrate a low quantitative accuracy, 90Y PET has been suggested as an alternative. The aim of this study is to quantitatively compare SPECT and state-of-the-art PET on the ability to detect small accumulations of 90Y and on the accuracy of liver dosimetry.

          Methodology/Principal Findings

          SPECT/CT and PET/CT phantom data were acquired using several acquisition and reconstruction protocols, including resolution recovery and Time-Of-Flight (TOF) PET. Image contrast and noise were compared using a torso-shaped phantom containing six hot spheres of various sizes. The ability to detect extra- and intrahepatic accumulations of activity was tested by quantitative evaluation of the visibility and unique detectability of the phantom hot spheres. Image-based dose estimates of the phantom were compared to the true dose. For clinical illustration, the SPECT and PET-based estimated liver dose distributions of five RE patients were compared. At equal noise level, PET showed higher contrast recovery coefficients than SPECT. The highest contrast recovery coefficients were obtained with TOF PET reconstruction including resolution recovery. All six spheres were consistently visible on SPECT and PET images, but PET was able to uniquely detect smaller spheres than SPECT. TOF PET-based estimates of the dose in the phantom spheres were more accurate than SPECT-based dose estimates, with underestimations ranging from 45% (10-mm sphere) to 11% (37-mm sphere) for PET, and 75% to 58% for SPECT, respectively. The differences between TOF PET and SPECT dose-estimates were supported by the patient data.

          Conclusions/Significance

          In this study we quantitatively demonstrated that the image quality of state-of-the-art PET is superior over Bremsstrahlung SPECT for the assessment of the 90Y microsphere distribution after radioembolization.

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          Most cited references25

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          Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium.

          To standardize the indications, techniques, multimodality treatment approaches, and dosimetry to be used for yttrium-90 (Y90) microsphere hepatic brachytherapy. Members of the Radioembolization Brachytherapy Oncology Consortium met as an independent group of experts in interventional radiology, radiation oncology, nuclear medicine, medical oncology, and surgical oncology to identify areas of consensus and controversy and to issue clinical guidelines for Y90 microsphere brachytherapy. A total of 14 recommendations are made with category 2A consensus. Key findings include the following. Sufficient evidence exists to support the safety and effectiveness of Y90 microsphere therapy. A meticulous angiographic technique is required to prevent complications. Resin microsphere prescribed activity is best estimated by the body surface area method. By virtue of their training, certification, and contribution to Y90 microsphere treatment programs, the disciplines of radiation oncology, nuclear medicine, and interventional radiology are all qualified to use Y90 microspheres. The panel strongly advocates the creation of a treatment registry with uniform reporting criteria. Initiation of clinical trials is essential to further define the safety and role of Y90 microspheres in the context of currently available therapies. Yttrium-90 microsphere therapy is a complex procedure that requires multidisciplinary management for safety and success. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies.
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            The sensitivity performance of the human eye on an absolute scale.

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              Efficacy and toxicity related to treatment of hepatocellular carcinoma with 90Y-SIR spheres: radiobiologic considerations.

              Radioactive (90)Y-selective internal radiation (SIR) sphere therapy is increasingly used for the treatment of nonresectable hepatocellular carcinoma (HCC). However, the maximum delivered dose is limited by severe injury to the nontarget tissue, including liver parenchyma. Our study aimed to implement radiobiologic models for both tumor control probability (TCP) and normal-tissue complication probability (NTCP) to describe more effectively local response and the liver toxicity rate, respectively. Patients with documented HCC, adequate bone marrow parameters, and regular hepatic and pulmonary function were eligible for the study. Patients who had pulmonary shunt greater than 20% of (99m)Tc-labeled macroaggregated albumin or any uncorrectable delivery to the gastrointestinal tract, reverse blood flow out of the liver, or complete portal vein thrombosis were excluded. Patients received a planned activity of the (90)Y-SIR spheres, determined using the empiric body surface area method. The dose distribution was determined using posttreatment (3-dimensional) activity distribution and Monte Carlo dose voxel kernel calculations, and the mean doses to healthy liver and tumor were calculated for each patient. Response was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) and recommendations of the European Association for the Study of the Liver (EASL). Criteria were used to assess possible liver toxicities. The parameters of TCP and NTCP models were established by direct maximization of the likelihood. Seventy-three patients were treated. With an average dose of 110 Gy to the tumor, complete or partial response was observed in 74% and 55% of patients according to the EASL guideline and RECIST, respectively, and the predicted TCPs were 73% and 55%, respectively. With a median liver dose of 36 Gy (range, 6-78 Gy), the >or=grade 2 (G2), >or=grade 3 (G3), and >or=grade 4 (G4) liver toxicities were observed in 32% (23/73), 21% (15/73), and 11% (8/73) of patients, respectively. The parameters describing the >or=G2 liver toxicity data using the NTCP model were a tolerance dose of the whole organ leading to a 50% complication probability of 52 Gy (95% confidence interval, 44-61 Gy) and a slope of NTCP versus dose of 0.28 (95% confidence interval, 0.18-0.60), assuming n = 1. The radiobiologic approach, based on patient-specific dosimetry, could improve the (90)Y-microsphere therapeutic approach of HCC, maintaining an acceptable liver toxicity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                6 February 2013
                : 8
                : 2
                : e55742
                Affiliations
                [1]Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
                University of Modena & Reggio Emilia, Italy
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ME BJV MGEHL HJ. Performed the experiments: ME BJV BdK MAAJvdB. Analyzed the data: ME BJV HWAMdJ. Contributed reagents/materials/analysis tools: ME BJV. Wrote the paper: ME BJV MGEHL BdK MAAJvdB HWAMdJ.

                Article
                PONE-D-12-24460
                10.1371/journal.pone.0055742
                3566032
                23405207
                945aa0d2-1ab1-4058-9f8f-b0c5051a3ca1
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 August 2012
                : 30 December 2012
                Page count
                Pages: 10
                Funding
                This work was funded by the University Medical Center Utrecht. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Gastroenterology and Hepatology
                Gastrointestinal Cancers
                Liver Diseases
                Oncology
                Cancer Treatment
                Radiation Therapy
                Radiology
                Nuclear Medicine
                PET imaging
                Radionuclide Imaging
                SPECT imaging
                Interventional Radiology
                Medical Physics

                Uncategorized
                Uncategorized

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