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Monitoring response to transarterial chemoembolization in hepatocellular carcinoma using 18F-Fluorothymidine Positron Emission Tomography

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Title: Monitoring response to transarterial chemoembolization in hepatocellular carcinoma using 18F-Fluorothymidine Positron Emission Tomography
Authors: Aboagye, E
Sharma, R
Inglese, M
Dubash, S
Lu, H
Pinato, D
Patel, N
Chung, A
Sanghera, C
Tait, A
Mauri, F
Crum, W
Barwick, T
Item Type: Journal Article
Abstract: Accurate disease monitoring is essential following transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) due to potential for profound adverse event and large variation in survival outcome. Post-treatment changes on conventional imaging can confound determination of residual/recurrent disease, magnifying the clinical challenge. Based on increased expression of thymidylate synthase (TYMS), thymidine kinase-1 (TK-1) and SLC29A1 (Equilibrative nucleoside transporter 1, ENT1) in HCC compared with liver tissue, we conducted a proof of concept study evaluating the efficacy of 18F-fluorothymidine (18F-FLT)-PET to assess response to TACE. As previous PET studies in HCC have been hampered by high background liver signal, we investigated if a temporal-intensity voxel-clustering (“Kinetic Spatial Filtering”) (KSF) improved lesion detection. Methods: A tissue microarray (TMA) was built from 36 HCC samples and matched surrounding cirrhotic tissue and was stained for thymidine kinase-1 (TK-1). A prospective study was conducted; eighteen patients with a diagnosis of HCC by American Association for the Study of Liver Diseases criteria (AALSD) who were eligible to treatment with TACE were enrolled. Patients underwent baseline conventional imaging and dynamic 18F-FLT-PET/KSF followed by TACE. Repeat imaging was performed 6-8 weeks post TACE. PET parameters were compared with modified-Response Evaluation in Solid Tumours (mRECIST) enhancement-based criteria. Results: Cancer Genome Atlas analysis revealed increased RNA expression of TYMS, TK-1 and SLC29A1 in HCC. TK-1 protein expression was significantly higher in HCC (p<0.05). The sensitivity of 18F-FLT-PET for baseline HCC detection was 73% (SUVmax of 9.7 ± 3.0; tumour to liver ratio of 1.2 ± 0.3). Application of KSF did not improve lesion detection. Lesion response following TACE by mRECIST criteria was 58% (14 patients with 24 lesions). A 30% reduction in mean 18F-FLT-PET uptake was observed following TACE correlating to an observed PET response of 60% (n = 15/25). A significant and profound reduction in radiotracer delivery parameter, K1, following TACE was observed. Conclusion: 18F-FLT-PET can differentiate HCC from surrounding cirrhotic tissue, with PET parameters correlating with TACE response. KSF did not improve visualization of tumour lesions. These findings warrant further investigation.
Issue Date: 1-Dec-2020
Date of Acceptance: 3-Apr-2020
URI: http://hdl.handle.net/10044/1/81637
DOI: 10.2967/jnumed.119.240598
ISSN: 0161-5505
Start Page: 1743
End Page: 1748
Journal / Book Title: The Journal of Nuclear Medicine
Volume: 61
Issue: 3/4/20
Copyright Statement: © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc. Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MR/J007986/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Radiology, Nuclear Medicine & Medical Imaging
F-18-FLT PET
hepatocellular cancer
response
POSITRON-EMISSION-TOMOGRAPHY
KINETIC-ANALYSIS
CELLULAR PROLIFERATION
DIFFERENTIATING TUMOR
C-11-ACETATE PET/CT
BREAST-CANCER
CHEMOTHERAPY
VALIDATION
F-18-FDG
MARKER
18F-FLT PET
hepatocellular cancer
response
Nuclear Medicine & Medical Imaging
1103 Clinical Sciences
Publication Status: Published
Online Publication Date: 2020-06-08
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine



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