Monitoring Response to Transarterial Chemoembolization in Hepatocellular Carcinoma Using (18)F-Fluorothymidine PET

Accurate disease monitoring is essential after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) because of the potential for profound adverse events and large variations in survival outcome. Posttreatment changes on conventional imaging can confound determination of residual or recurrent disease, magnifying the clinical challenge. On the basis of increased expression of thymidylate synthase (TYMS), thymidine kinase 1 (TK-1), and equilibrative nucleoside transporter 1 (SLC29A1) in HCC compared with liver tissue, we conducted a proof-of-concept study evaluating the efficacy of 3′-deoxy-3′-(18)F-fluorothymidine ((18)F-FLT) PET to assess response to TACE. Because previous PET studies in HCC have been hampered by high background liver signal, we investigated whether a temporal-intensity voxel clustering (kinetic spatial filtering, or KSF) improved lesion detection. Methods: A tissue microarray was built from 36 HCC samples and from matching surrounding cirrhotic tissue and was stained for TK-1. A prospective study was conducted; 18 patients with a diagnosis of HCC by the criteria of the American Association for the Study of Liver Diseases who were eligible for treatment with TACE were enrolled. The patients underwent baseline conventional imaging and dynamic (18)F-FLT PET with KSF followed by TACE. Imaging was repeated 6–8 wk after TACE. The PET parameters were compared with modified enhancement-based RECIST. 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 (18)F-FLT PET for baseline HCC detection was 73% (SUV(max), 9.7 ± 3.0; tumor to liver ratio, 1.2 ± 0.3). Application of KSF did not improve lesion detection. Lesion response after TACE by modified RECIST was 58% (14 patients with 24 lesions). A 30% reduction in mean (18)F-FLT PET uptake was observed after TACE, correlating with an observed PET response of 60% (15/25). A significant and profound reduction in the radiotracer delivery parameter K(1) after TACE was observed. Conclusion: (18)F-FLT PET can differentiate HCC from surrounding cirrhotic tissue, with PET parameters correlating with TACE response. KSF did not improve visualization of tumor lesions. These findings warrant further investigation.