11C-Acetate uptake on Positron Emission Tomography (PET) as a novel biomarker for hypoxic gene expression in Hepatocellular Carcinoma (HCC) – a preclinical study.

Abstract

Aims and objectives Primary Liver cancer (Hepatocellular Carcinoma, HCC) is the 3 rd leading cause of cancer-related mortality worldwide (1). Over the past decade, combined 11 C-acetate and 2-deoxy-2-( 18 F)fluoro-D-glucose ( 18 F-FDG) dual-tracer Positron-Emission Tomography-Computed Tomography (PET-CT) has been found not only to be highly sensitive (approaching 100%) in detecting HCC but also to be predictive of histological grade, disease recurrence and overall survival (2-5). Although it has been routinely... Methods and materials Orthotopic mice xenografts were created using MHCC97L cell line as previously described (6,7). MHCC97L cells (~6 ×10 5 ) suspended in 0.2ml culture medium were injected subcutaneously into the right flank of each athymic nude mice (BALB/c nu/nu, 6 weeks old). Once tumors reached 0.5~0.8cm in dimension, they were harvested and cut into small blocks (~1mm 3 ). Each of these tumor blocks was then transplanted into the liver of another athymic nude mouse, with or without hepatic artery ligation... Results Ten mice xenografts were created, with 5 undergone additional hepatic artery ligation (HAL) during implantation. 11 C-acetate uptake was significantly lower in the HAL group (median tumor-to-background ratio 2.41 vs. 3.61, p=0.008) while no difference was seen in tumor volume or 18F-FDG uptake (Figure 1). Differential gene expression analysis of the HAL compared with the control groups showed significant upregulation in the non-canonical Wnt pathway gene WNT5A (Fold change =1.7, adjusted... Conclusion 11 C-acetate uptake in PET is associated with upregulation of hypoxia pathways. It has the potential to be a non-invasive biomarker for patients with HCC for identifying underlying hypoxic gene signatures. Read more