[68Ga]DOTATATE-PET/MRI in Hepatocellular Carcinoma

There is great need for new therapeutic options for patients with hepatocellular carcinoma
(HCC). This proposal will assess the feasibility of a novel theranostic approach to HCC using
[68Ga]DOTATATE, a recently approved positron emission tomography (PET) ligand for imaging
somatostatin receptor (SSTR) positive tumors. In this study, we will use [68Ga]DOTATATE to
determine the percentage of HCCs that express adequate levels of SSTR for treatment with
targeted radionuclide therapy (TRT) using the therapeutic SSTR ligand [177Lu]DOTATATE. This
radionuclide therapy was FDA approved in January 2018 for treating neuroendocrine tumors
(NETs) arising from the gastrointestinal tract, but its use in HCC has not yet been explored.
In the long term, we envision using [68Ga]DOTATATE-PET to identify HCC patients with adequate
SSTR expression for TRT using [177Lu]DOTATATE.

Liver transplantation is the only curative therapy for HCC and is an option for a selected
subset of HCC patients. For those who are not candidates for transplantation, locoregional
therapies with limited efficacy are available such as percutaneous ablation, arterial
chemoembolization, and Y-90 microsphere radionuclide therapies. There are few options for
patients who progress or are not candidates for these therapies. The first line systemic
therapy is sorafenib, a tyrosine kinase inhibitor. Sorafenib is often not well tolerated due
to its side effects and there is need for additional systemic treatments. Multiple
tissue-based studies demonstrate SSTR positivity in 20-50% of HCCs.[1-3] However, the
fraction of HCCs have high enough levels of SSTR for [177Lu]DOTATATE therapy has not yet been
assessed. This research plan is a critical prerequisite for determining the feasibility of
this theranostic approach to treating HCC. If we obtain positive results, these data will be
critical for designing a combined imaging and therapeutic study in HCC using DOTATATE.