Comparison of (11)C-Acetate and (18)F-FDG PET/CT for Immune Infiltration and Prognosis in Hepatocellular Carcinoma.

Immunotherapy has revolutionized cancer treatment, making it a challenge to noninvasively monitor immune infiltration. Metabolic reprogramming in cancers, including hepatocellular carcinoma (HCC), is closely linked to immune status. In this study, we aimed to evaluate the ability of carbon-11 acetate ((11)C-acetate) and fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET/CT findings in predicting overall survival (OS) and immune infiltration in HCC patients. Totally 32 patients who underwent preoperative (18)F-FDG and (11)C-acetate PET/CT, followed by liver resection for HCC, were prospectively enrolled at authors' institute between January 2019 and October 2021. Tracer uptake was qualified. Densities of CD3(+), CD8(+), and granzyme B(+) CD8(+) immune cells were assessed and the Immunoscore was defined by combining the densities of CD3(+) and CD8(+) in tumor interior (TI) and invasion margin (IM). Patients with avid HCCs in (11)C-acetate PET/CT demonstrated a longer OS. Those with only (11)C-acetate-avid HCCs exhibited a longer OS compared to those with only (18)F-FDG uptake. In contrast to (18)F-FDG uptake, (11)C-acetate uptake was positively associated with CD3(+), CD8(+), and granzyme B(+) CD8(+) cell infiltration. Patients with a higher Immunoscore exhibited a longer OS and an increased uptake of (11)C-acetate rather than (18)F-FDG. The sensitivity of (11)C-acetate PET/CT in the detection of patients with immune infiltration was superior to that of (18)F-FDG PET/CT (88% [21 of 24] vs. 58% [14 of 24]). These data show that preoperative (11)C-acetate PET/CT may be a promising approach for the evaluation of immune status and postoperative outcome of HCCs.