This is a single-arm, open-label, single-center, first-in-human feasibility study evaluating parenchymal blood volume (PBV) imaging as a tool to dynamically assess perfusional changes in hepatocellular carcinoma (HCC) potentiated by intra-arterial administration of nitroglycerin.

PRIMARY OBJECTIVES:

I. Evaluate in vivo, parenchymal blood volume imaging's ability to dynamically assess blood flow to hepatocellular carcinoma.

SECONDARY OBJECTIVES:

1. Quantitative measurement of tumor perfusion after intra-arterial injection of nitroglycerin using parenchymal blood volume imaging.

OUTLINE:

Participants will undergo parenchymal blood volume (PBV) imaging before and after intra-arterial nitroglycerin injection during their standard transarterial chemoembolization (TACE) treatment. Participants will be followed on days 3, 7, 30, and 90 after the procedure.

Inclusion Criteria:

1. Participants must have radiographically documented, previously untreated LIRADS V liver lesions or biopsy-confirmed hepatocellular carcinoma (HCC), as determined by the ZSFG Liver Tumor Board.

2. Lesions must be determined to be suitable for conventional trans-arterial chemoembolization (cTACE) based on multidisciplinary tumor board review.

3. No prior locoregional therapy (e.g., TACE, Y-90) to the index lesion(s).

4. Age ≥18 years.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky >70%)

6. Demonstrates adequate organ function as defined below:

   1. Absolute neutrophil count >=1,500/microliter (mcL).
   2. Platelets ≥100,000/microliter (mcL).
   3. Total bilirubin ≤ 3.0 milligrams per deciliter (mg/dL), unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
   4. Aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) ≤3 X institutional upper limit of normal.
   5. Alanine aminotransferase (ALT) / serum glutamic-oxaloacetic transaminase (SGPT) ≤3 X institutional upper limit of normal
   6. Creatinine ≤ 1.5 x within institutional upper limit of normal or
   7. Creatinine clearance Glomerular filtration rate (GFR) >= 60 milliliters per minute (mL/min)/1.73 m2, calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 milliliters per minute (mL/min)/1.73 m2.

7. Liver function: Child-Pugh score must be no higher than B5.

8. Ability to understand and the willingness to sign a written informed consent document.

9. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

10. The female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception during the study and for 30 days after study intervention.

Exclusion Criteria:

1. Multifocal disease (i.e., presence of more than one HCC lesion).

2. Has received systemic anticancer therapies within 3 weeks of first dose, radiation within 2 weeks, antibody therapy within 4 weeks. Concomitant administration of LHRH analogues for prostate cancer and somatostatin analogues for neuroendocrine tumors are allowed as per standard of care.

3. Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia).

4. Is currently receiving any other therapeutic/investigational agents.

5. Has participated in a study of an investigational product and received study treatment or used an investigational device within 3 weeks of the first use of an investigational product.

6. Co-morbid disease or concurrent illness (e.g., cardiovascular disease, portal vein thrombosis).

7. Hypersensitivity to nitroglycerine or any of its excipients.

8. Concomitant medications (contraindicated):

   1. Concurrent use of prescription phosphodiesterase inhibitors (e.g., sildenafil)
   2. Concurrent use of nitrate-containing medications.
   3. Concurrent use of vasoactive chemotherapeutic agents, such as bevacizumab (Avastin).

9. Recent anti-cancer therapies:

   1. Systemic anticancer therapies within 3 weeks of the procedure.
   2. Radiation therapy within 2 weeks.
   3. Antibody-based therapy within 4 weeks.
   4. Use of investigational agents or devices within 3 weeks of the index procedure.

10. Unresolved toxicities from prior cancer therapy, unless ≤ Grade 1 (excluding alopecia).

11. Currently receiving any other therapeutic or investigational agents during the study period.