This early phase I trial evaluates the use of hypoxia (lack of oxygen) as a measure in determining the outcome of Y90 selective internal radiation therapy in patients with liver cancer that has spread to a limited number of sites (oligometastatic). Radioembolization with Y90 is a minimally invasive procedure that combines embolization and radiation therapy to treat metastatic liver cancer. Tiny beads filled with radioactive isotope Y-90 are placed inside the blood vessel that provide blood supply to the tumor. This will block the blood flow to the tumor cells while providing a high radiation dose without harming healthy normal tissue.

PRIMARY OBJECTIVE:

I. To investigate the variability of hypoxia in hepatocellular carcinoma (HCC) as quantified by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and dynamic 18F-Fluoromisonidazole (FMISO) positron emission tomography (PET).

SECONDARY OBJECTIVES:

I. Investigate whether hypoxia, as quantified by BOLD MRI, dynamic FMISO PET, HIF-1alpha and VEGF expression, predicts HCC response to yttrium-90 (Y90) selective internal radiation therapy (SIRT).

II. Assess whether hypoxia quantification by BOLD MRI, dynamic FMISO, HIF-1alpha or VEGF expression individually or in combination more accurately predict the degree of HCC tumor response to Y90 SIRT.

III. Compare the tumor dose response threshold between hypoxic and non-hypoxic HCCs treated with Y90 SIRT.

OUTLINE:

Patients receive 18F-fluoromisonidazole intravenously (IV) and undergo PET and dynamic contrast enhanced (DCE) MRI within 30 days before beginning Y90 SIRT. Patients undergo Y90 SIRT per standard of care.

After completion of study intervention, patients are followed up at 90 days, and then every 12 weeks thereafter.

Inclusion Criteria:

• Age >= 18 years
• Established HCC diagnosis, unilobar or bilobar disease
• At least 1 tumor >= 3 cm
• Oligometastatic disease
• Barcelona Clinic Liver Cancer (BCLC) stage A, B or C
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy > 12 weeks as determined by the Investigator
• The effects of Y90 Radioembolization on the developing human fetus are unknown. For this reason, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
• FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months

Exclusion Criteria:

• Patients who are definite transplant candidates
• Concurrent second malignancy outside of the liver
• Infiltrative liver tumor
• Previous liver-directed therapy to targeted tumors
• BCLC stage D
• Bilirubin > 2 mg/dL for lobar treatment and bilirubin > 3 mg/dL for segmental or bi-segmental Y90-SIRT
• Albumin < 3 g/dL
• Projected lung dose of > 30 Gy in a single session to the liver after prospective treatment planning
• Body mass index (BMI) > 40