# DNP-MRSI for the Detection of Latent, Treatment-Resistant Cellular Domains in HCC

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $416,075

## Abstract

Established guidelines for assessing response of solid tumors to therapy are based on conventional imaging
indices, such as tumor size and vascularity, and were intended to facilitate a uniform assessment of response to
systemically administered chemotherapeutics that target proliferating cells in a well-perfused microenvironment.
An emerging imaging phenotype of tumor recurrence indicates that a complete radiographic response may be
followed by variable periods of latency without perceptible growth in poorly perfused microenvironments. This
imaging phenotype highlights the capability of cancer cells to adapt their growth program to their
microenvironment and effect tumor dormancy and underscores the importance of developing functional imaging
paradigms to enable their detection.
Transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) provides a
compelling clinical correlate to this imaging deficiency. TACE exploits the vascular biology of HCC to deprive
tumors of nutrients, leading to necrosis; however, only 44% of large treated lesions demonstrate extensive
necrosis on pathology, underscoring the adaptive response of HCC cells to nutrient deprivation. This adaptive
response is reflected by the presence of viable tumor cells adjacent to regions of necrosis on histopathology,
and is consistent with the rapid recurrence following a period of latency often observed on follow-up imaging. In
preclinical studies, we demonstrated that: 1) HCC cells surviving TACE-induced ischemia are reprogrammed to
shunt glucose carbons toward lactate, providing a unique signature for the detection of these cells; 2) based on
this reprogramming, Dynamic Nuclear Polarization Magnetic-13Carbon-Magnetic Resonance Spectroscopic
Imaging (DNP-13C-MRSI)of hyperoplarized (HP) 1-13C-pyruvate enables the more sensitive detection of HCC
cells for response assessment to TACE as compared to standard-of-care (SOC) MRI; and 3) the detection of
TACE-refractory cellular domains will inform targeted therapy by identifying molecular dependencies.
We hypothesize that DNP-13C-MRSI of HP 1-13C-pyruvate provides a unique technology through which to
leverage the metabolic reprogramming in HCC cells surviving TACE and enable functional molecular imaging
for effective treatment response assessment in patients. To test this hypothesis the proposed project will pursue
two primary aims: (1) to validate an optimized pulse sequence for in vivo hepatic arterial phase DNP-13C-MRSI
of HP 1-13C-pyruvate in HCC using clinical imaging systems.; (2a) to determine the sensitivity of DNP-13C-MRSI
of HP 1-13C-pyruvate uptake and metabolism for identifying local recurrence in patients with a complete response
to TACE, as measured by current SOC imaging response criteria; and (2b) to determine the accuracy of DNP-
13C-MRSI of HP 1-13C-pyruvate to lactate and alanine for the detection of the targetable metabolic stress
response in HCC cells following TACE. The achievement of t...

## Key facts

- **NIH application ID:** 10436006
- **Project number:** 1R21CA263364-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Terence P Gade
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $416,075
- **Award type:** 1
- **Project period:** 2022-09-09 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436006

## Citation

> US National Institutes of Health, RePORTER application 10436006, DNP-MRSI for the Detection of Latent, Treatment-Resistant Cellular Domains in HCC (1R21CA263364-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10436006. Licensed CC0.

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