Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population

Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[F-18]fluoropropyl)-L-glutamic acid ([F-18]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [F-18]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [C-11]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [F-18]FSPG PET/CT and present the first comparison to [C-11]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. x(C-) transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [F-18]FSPG PET/CT, with seven patients also imaged with [C-11]acetate PET/CT. x(C-) transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and similar to 70 % of high-grade tumors exceeded background liver protein expression. [F-18]FSPG PET/CT demonstrated a detection rate of 75 %. [F-18]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [F-18]FSPG and [C-11]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [F-18]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [C-11]acetate PET/CT. [F-18]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [F-18]FSPG PET/CT impact on diagnosis and management of HCC. [F-18]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.