# Novel PET Imaging to Guide Therapy in Hepatocellular Carcinoma

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $678,515

## Abstract

PROJECT SUMMARY/ABSTRACT: Novel PET Imaging to Guide Therapy in Hepatocellular Carcinoma
Liver cancer is the third leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC)
constituting more than 75% of all liver cancers. Locoregional therapies (LRTs), such as transcatheter arterial
radioembolization (TARE) with Yttrium-90 (Y90), play a critical role in the care of patients with HCC. For patients
undergoing LRT, time is of the essence; the time required to determine how an HCC responds to LRT is a critical
determinant in the overall care algorithm and outcome for these patients. Current methods to predict response
to Y90 LRT rely on standard-of-care (SOC) anatomical imaging, such as magnetic resonance imaging (MRI) or
computed tomography (CT), which remain ambiguous for months following treatment. During this critical waiting,
physicians and patients face uncertainty with respect to disease status, with eligibility for future interventions
frequently compromised by ambiguities associated with determining treatment outcomes.
 In this project, we propose to evaluate an innovative molecular imaging approach to predict response to
Y90 LRT much earlier than SOC imaging. We have previously evaluated 18F-FSPG PET in liver cancer and
found it to be highly suitable for lesion detection and evaluation of response to therapy. Cancer cell accumulation
of 18F-FSPG is mediated by xCT (SLC7A11) transporter activity, which is highly correlated with resistance to
radiation. Thus, we hypothesize that 18F-FSPG PET represents an ideal biomarker to predict the response of
HCC to Y90 LRT at baseline or soon after therapy, to identify residual, Y90-resistant disease and early
recurrence. Complementary to imaging, liquid biopsy involves the collection of blood or other body fluids for the
detection of tumor-derived molecular specimens, including circulating tumor cells (CTCs) and circulating tumor
DNA (ctDNA). In this application, we propose to determine if ctDNA levels are actionable in the setting of patients
with HCC undergoing Y90 LRT, triggering future 18F-FSPG PET/CT examinations in these patients.
 Our overall objective is to evaluate 18F-FSPG PET as a means to predict early response and recurrence
following Y90 therapy and to determine whether PET imaging and ctDNA are correlated. Our overarching
hypothesis is that 18F-FSPG PET will predict response to Y90 therapy and tumor recurrence sooner than
standard-of-care (SOC) imaging and will be highly correlated with ctDNA liquid biopsy. We will test our
hypothesis, in two Specific Aims. Aim 1. To evaluate the relationship between 18F-FSPG uptake in HCC lesions,
ctDNA in blood, and clinical response to Y90 radioembolization therapy by SOC imaging. Aim 2. To evaluate
voxel-wise correlations between post-treatment 18F-FSPG intra-tumoral accumulation and SOC imaging in
patients with HCC who have undergone TARE.
Clinical Impact: This study holds the potential to improve HCC disease management by providi...

## Key facts

- **NIH application ID:** 10980028
- **Project number:** 1R01CA279467-01A1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Henry Charles Manning
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $678,515
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980028

## Citation

> US National Institutes of Health, RePORTER application 10980028, Novel PET Imaging to Guide Therapy in Hepatocellular Carcinoma (1R01CA279467-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980028. Licensed CC0.

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