This phase II trial studies how well 68Ga-PSMA PET/MRI or PET/CT works in early detection of liver cancer. 68Gallium-PSMA is a radioactive tracer designed to circulate through the body and attach itself to the prostate- specific membrane antigen (PSMA) protein on liver cancer cells. Magnetic resonance imaging (MRI) is a scan that uses magnetic and radio waves to produce detailed structural information of the organs, tissues, and structures within the body. Positron emission tomography (PET) is an imaging test that helps to measure the information about functions of tissues and organs within the body. A PET scan uses a radioactive drug (tracer) to show this activity. Computed tomography (CT) scan uses X-rays to create images of the bones and internal organs within your body. Combining a PET scan with an MRI or CT scan may help make the images easier to interpret. This trial may help determine if 68Ga- PSMA PET/MRI or PET/CT can improve upon the diagnosis and management of liver cancer in the future.

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and diagnostic performance of gallium Ga 68 gozetotide (68Ga PSMA)-dual contrast PET/MRI for detection and staging of hepatocellular carcinoma (HCC), and to compare it with standard-of-care (SOC) imaging.

II. To identify the biologic correlates of biomarkers derived from 68Ga PSMA-dual contrast PET/MRI with histopathology features and PSMA immunostaining of HCC.

OUTLINE:

Patients receive 68Ga-PSMA intravenously (IV) over 90 minutes. Patients then undergo PET/MRI over 60 minutes or PET/CT over 30 minutes.

Inclusion Criteria:

• Patients with either an imaging diagnosis of Hepatocellular carcinoma (HCC) by Computed Tomography (CT) or Magnetic Resonance Imaging MRI (Liver Imaging Reporting and Data System [LI-RADS] 5) confirmed by a board-certified abdominal radiologist, or with biopsy-proven HCC
• Subjects who may undergo hepatic surgical resection, liver transplant, or hepatic locoregional therapy (LRT) (e.g., ablation, embolization, etc.)
• No prior treatment for index HCC lesion (surgical resection, liver transplant, hepatic locoregional therapy arm). Patients that have been previously treated with HCC, but have new or reoccurring untreated lesions, are included in the study.
• Male or female with age greater than 18 years, with the capacity and willingness to provide written informed consent.

Exclusion Criteria:

• Patients requiring emergent surgery for a ruptured/bleeding HCC

• Bilirubin > 3.0 mg/dL, which is a contraindication for Gadoxetate, the MRI contrast agent (relevant to positron emission tomography [PET]/MRI)

• Patients with glomerular filtration rate (GFR) < 30 ml/min/1.73m^2, on dialysis, or with acute kidney injury

• Pregnant and/or breast-feeding patients. A negative pregnancy test within 48 hours of the PET scan

• Patients with higher than the weight/size limitations of PET/MRI or PET/CT scanner

• Subjects with history of allergic response to Eovist or Gadavist

• Subjects with known history of claustrophobia

• Subjects with GFR < 30 ml/min/1.73m^2, on dialysis, or with acute kidney injury

• Subjects with a history of severe hypersensitivity to Eovist or Gadavist

• Patients with contraindication to MRI (relevant to PET/MRI):

  • Patients who have a heart pacemaker
  • Patients who have a metallic foreign body (metal sliver) in their eye, or who have an aneurysm clip in their brain
  • Patients who have implanted devices with magnets
  • Patients who have other implanted electronic devices
  • Patients who have deep brain stimulator
  • Patients who have vagal nerve stimulator
  • Patients with cochlear (ear) or auditory implants

PSMA PET/CT will be an alternative in this study for patients who are unable to undergo PET/MRI for any reason but are otherwise eligible for the study.