What this trial measures

• 18F-FSPG PET standardized uptake value (SUV)Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy

  The Standardized Uptake Value (SUV) for 18F-FSPG PET images will be determined in the hepatocellular carcinoma (HCC) tumor lesions, non-HCC liver tumors (benign), and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.

• 11C-acetate standardized uptake value (SUV)Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy

  The Standardized Uptake Value (SUV) for 11C-acetate PET images will be determined in the tumor lesions and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.

• 18F-FDG standardized uptake value (SUV)Within 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy

  The Standardized Uptake Value (SUV) for 18F-FDG PET images will be determined in the hepatocellular carcinoma (HCC) tumor lesions and background liver (normal tissue). These metrics include SUVmax, SUVpeak, or SUVmean and are common PET imaging measures.

• Pharmacokinetics of 18F-FSPG, 11C-acetate, and 18F-FDGWithin 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy

  The pharmacokinetics of 18F-FSPG, 11C-acetate and 18F-FDG uptake will be determined using compartmental modeling of PET imaging data. Venous samples will be collected over the course of 18F-FSPG, 11C-acetate and 18F-FDG scans to confirm blood pool radioactivity, evaluate metabolism, and to calibrate image-derived input functions. We will also utilize blood samples collected prior to scanning to assay plasma levels of carbon-12 acetate and glucose in each patient to explore normalizing pharmacokinetic parameters across patients.

• Number of lesionsWithin 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy

  The number of lesions detected by 18F-FSPG PET will be determined and compared to the number of lesions detected by standard-of-care MRI, 11C-acetate PET, or 18F-FDG PET on a per patient basis.

• Sensitivity of 18F-FSPG PET imagingWithin 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy

  Sensitivity is defined as the true positive rate. It is defined as true positive/(true positive + false negative). The determination of HCC status will be based on diagnostic pathology.

• Specificity of 18F-FSPG PET imagingWithin 4 weeks of standard-of-care imaging, within 4 weeks of liver resection surgery, within 12 months of orthotopic liver transplant and prior to therapy

  Specificity is defined as the true negative rate. It is defined as true negative/(true negative + false positive). The determination of HCC status will be based on diagnostic pathology.

• Diagnostic pathologyAfter surgery; Through study completion, up to 4 years

  Tissue samples will be obtained for patients following either liver resection surgery or orthotopic liver transplant. Pathology will be performed on these tumor tissues as the gold-standard assessment to confirm the presence of HCC tumor. Histology will be correlated to PET imaging data.

• Tumor gradeAfter surgery; Through study completion, up to 4 years

  Tissue samples will be obtained for patients following either liver resection surgery or orthotopic liver transplant. Tumor grade will be determined from pathology of tissue samples and correlated to PET imaging data for 18F-FSPG, 11C-acetate and 18F-FDG PET. The concordance of 18F-FSPG PET/CT and 11C-acetate PET/CT or 18F-FSPG PET/CT and 18F-FDG PET/CT will be evaluated. This will determine whether 18F-FSPG can be used singularly in place of combined use of 11C-acetate PET/CT (which typically detects low grade HCC) and 18F-FDG PET/CT (which typically detects high grade HCC).

• ImmunohistochemistryAfter surgery; Through study completion, up to 4 years

  Tissue samples will be obtained for patients following liver resection surgery. The expression of immunohistochemical markers (ie. xC- and CD44) will be evaluated in these tumor tissues on an ordinal scale of 0, 1, 2 or 3 and correlated to 18F-FSPG PET imaging data. In addition, markers of inflammation and immune cell recruitment (ie. CD86, CD163, CD3), proliferation (Ki67), and apoptosis (Caspase 3) will also be evaluated and correlated to 18F-FSPG PET imaging data.