# Noninvasive High-Resolution Mapping of HCC Tumor Biology Predictive of Malignancy

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $657,105

## Abstract

PROJECT ABSTRACT: Hepatocellular carcinoma (HCC) is an aggressive malignancy representing the 7th most
common cancer globally and the 4th most common cause of cancer death worldwide. Although magnetic
resonance imaging (MRI) represents a common HCC diagnostic and prognostic tool, MRI fails to provide insights
into HCC risk stratification, and does not allow for rational therapeutic allocation. Chemical exchange saturation
transfer (CEST) molecular MRI, on the other hand, permits noninvasive measurement of tumor metabolism
predictive of malignancy. Integration of CEST MRI into clinical HCC management has the potential to radically
alter clinical practice paradigms through: (1) identification of small malignant nodules and those with
unconventional enhancement features to increase diagnostic performance; (2) improved prediction of tumor
aggressiveness to inform patient prognosis and treatment stratification; and (3) monitoring of tumor metabolism
in patients post therapy to differentiate between pseudoprogression—characterized by tumor regression
following an initial increase in tumor burden—and true tumor progression. This proposal employs the innovative
Oncopig Cancer Model—a transgenic porcine model that recapitulates human cancer through induced KRASG12D
and TP53R167H expression—to test the hypothesis that noninvasive mapping of in vivo creatine (Cr) metabolism
empowers prediction of differential HCC tumor aggressiveness. Combining our innovative Oncopig Cancer
Model with MRI and CRISPR protocols optimized under our previously funded R03 and R21 grants, we will
image Oncopig HCC tumors engineered to display differential Cr metabolism and malignant potential to
demonstrate that Cr CEST MRI can accurately differentiate: 1) HCC malignancy due to intertumor genetic
heterogeneity, 2) intratumor heterogeneity, and 3) pseudoprogression from true tumor progression. Genes
targeted will include the ubiquitous mitochondrial Cr kinase (CKMT1), which converts ATP and Cr to ADP and
phosphocreatine to meet cellular energy demands. CKMT1 knockdown reduces human HCC proliferation and
migration in vitro, while increased CKMT1 serum levels are associated with poor prognosis following
radiofrequency ablation. We plan to test our hypothesis by pursuing the following specific aims: (1) Demonstrate
applicability of Cr CEST MRI for stratifying HCC malignancy reflective of intertumor genetic heterogeneity. (2)
Demonstrate applicability of Cr CEST MRI for assessment of intratumor heterogeneity. (3) Demonstrate
applicability of Cr CEST MRI to differentiate between pseudoprogression and true tumor progression. Oncopig
HCC tumor growth and Cr levels will be quantified using a respiratory gated liver CEST MRI protocol to reduce
motion artifacts. MRI-guided biopsy collection will enable co-registration—based comparison of in vitro
measurements with Cr CEST for assessment of Cr CEST sensitivity and specificity. This proposal will radically
alter HCC clinical practice paradigm...

## Key facts

- **NIH application ID:** 10878544
- **Project number:** 1R01CA283548-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Kejia Cai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $657,105
- **Award type:** 1
- **Project period:** 2024-03-11 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878544

## Citation

> US National Institutes of Health, RePORTER application 10878544, Noninvasive High-Resolution Mapping of HCC Tumor Biology Predictive of Malignancy (1R01CA283548-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10878544. Licensed CC0.

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