A Study to Assess the Effect of Y-90 Therapy on Non-target/Background Liver

Little is known on the potential relationship between Y-90 liver therapy and liver damage
this subject. Present assumptions and calculations of Y-90 administration are based on
surgical lobar hepatectomies and external radiation beam therapies.

As most participants that need Y90 based liver therapies have compromised livers, the
importance of knowing what potential collateral liver damage could be induced by Y90 is key
so as not induce liver failure. Successful treatment of a liver malignancy would not be
important if the potential mortality/morbidity risk of the treatment is higher or equal to
the existing malignancy.

As apposed to anatomical imaging looking for changes in size/shape which are late changes,
the investigators hope that by using a functional model of the liver, which can show early
changes of liver damage, the investigators can improve the sensitivity for detection of liver
damage and bridge this important knowledge gap. Additionally due to compensatory hypertrophy
of the non treated liver, potential liver damage estimated by lab tests may be masked, again
this emphasizes the importance of the measurement of the functional approach before and after
therapy.

The investigators will be enrolling participants planning to receive Y-90 therapy for the
treatment of liver malignancies. The diagnosis of a primary liver cancer, hepatocellular
carcinoma (HCC), is usually made by a combination of specific imaging findings and clinical
criteria; only rarely is a confirmatory biopsy performed. This is due to the high accuracy of
the present diagnostic model and the significant risk of biopsy and tumor seeding.

Y-90 therapy involves administering radioactive particles to liver tumors by placing a
catheter in a hepatic artery supplying the tumor using angiographic techniques and injection
of these particles.

Y-90 PET/CT imaging has been established as a method to validate and quantitate distribution
of Yttrium after Y-90 administration. The post Y-90 therapy PET/CT images provide an imaging
distribution of the Y-90, which is essential for validation of administered versus planned
dose to the liver lesion and background liver.

The investigators will be performing both specialized nuclear medicine HIDA and MRI scans
aimed at constructing a functional map of the liver before and 3 months after therapy.

The investigators will compare the Y-90 distribution to estimate background liver radiation
distribution and dose (generated by the Y-90 PET/CT scan) combined with the global and
regional function map (generated by the HIDA and MRI scans performed before and after
therapy), then the investigators will be assuming that the difference pre and post therapy in
global and regional function can be ascribed to the Y-90 administration.

The investigators will also analyze the MRI and NM data sets performed before and after
therapy and correlate the imaging results collected with clinical findings such as
ascites/encephalopathy and routine serological markers (bilirubin, albumin, INR, etc.).

With this information, the investigators will have the potential to establish whether there
is a relationship between Y-90 distribution to non-tumoral (normal) hepatic parenchyma and
the incidence and severity of REILD. This would have the potential to improve selection
criteria and outcomes in populations selected for Y-90 therapy in the future.

Inclusion Criteria:

1. Subjects must have the ability to understand and the willingness to sign a written
informed consent document.

2. Subjects must be ≥ 18 years of age at the time of signing informed consent.

3. Subjects must have a diagnosis of hepatocellular carcinoma (HCC) and a treatment plan
to undergo radioembolization therapy with Y-90 at Indiana University Health Hospital.

4. Subjects must be willing and able to comply with all procedures and visits required
for this protocol (pre-treatment, during treatment, and post-treatment).

Exclusion Criteria:

1. Subjects who have contraindications for receiving Y-90 therapy and any routine
procedures and imaging associated with Y-90 therapy, including subjects who are
pregnant or are planning to become pregnant, will not be eligible to participate in
this study. Female subjects who are of childbearing potential should inform her
treating physician should she become pregnant at any time during the course of the
study.

2. Subjects with contraindications for receiving hepatobiliary scans (HIDA scans) and
Magnetic Resonance Imaging (MRI scans) will not be eligible to participate in this
study.