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

Abstract

Purpose 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-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [18F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [11C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [18F]FSPG PET/CT and present the first comparison to [11C]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. Procedures xC− 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 [18F]FSPG PET/CT, with seven patients also imaged with [11C]acetate PET/CT. Results xC− transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [18F]FSPG PET/CT demonstrated a detection rate of 75 %. [18F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [18F]FSPG and [11C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [18F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [11C]acetate PET/CT. Conclusions [18F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [18F]FSPG PET/CT impact on diagnosis and management of HCC. [18F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.

Initial evaluation of (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (FSPG) PET/CT imaging in patients with head and neck cancer, colorectal cancer, or non-Hodgkin lymphoma

“…[ 18 F]FSPG did not accumulate in the inflammatory model tested in animals [16], although subsequent clinical studies reported uptake in sarcoidosis [19]. Pilot clinical studies examining dosimetry and biodistribution in healthy volunteers [20,21] and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results and confirmed preclinical data [22][23][24][25]. In particular, low background uptake in the brain, lung, and bowel was observed.…”

Cell-surface marker discovery for lung cancer

“…We have recently developed monoclonal antibody agents against both CA9 and CA12 [ 25 ], there are numerous reports of CA9 targeted imaging agents [ 35 – 58 ], and there is a commercially available near-infrared (NIR) fluorescent carbonic anhydrase inhibitor-based agent (Hypoxisense, PerkinElmer). Two 18 F-glutamate derivative PET agents and an 18 F-aminosuberic acid derivative PET agent have also been developed that target the x C - transporter (SLC7A11) [ 62 – 69 ]. Recently, a fluorescent cystine derivative has also been developed for imaging the x C - transporter (SLC7A11) [ 70 ].…”

Metabolic Imaging of Glutamine in Cancer

“…is an L-glutamate derivative that is specifically taken up by system Xc in tumor models and cancer patients (27)(28)(29). A similar tracer targeting the Xc transporter system, 5-18 F-fluoro-aminosuberic acid, also demonstrated potential usefulness as a tracer for monitoring of upregulation of system Xc transporter and oxidative stress (30).…”