# Targeting Neuroendocrine Prostate Cancer Using Multi-Probe Hyperpolarized 13C MRI for Improved Treatment and Therapeutic Monitoring

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $655,889

## Abstract

PROJECT SUMMARY / ABSTRACT
The goal of this image-guided drug delivery (IGDD) proposal is to overcome the translational barrier, as stated
in PAR-16-044, to create a new quantitative imaging approach providing improved characterization of the
cancer target for better drug selection and delivery, as well as improving real-time monitoring of whether the
drug target was effectively treated. This will be accomplished by using a novel dual-probe (13C pyruvate and
13C glutamine) hyperpolarized (HP) 13C metabolic imaging technique to discriminate biologically divergent
treatment-emergent neuroendocrine prostate cancer (NEPC) from advanced adenocarcinoma based on the
metabolic profile of NEPC tumors and to use real-time changes in metabolism to monitor the drug's delivery
and efficacy. NEPC is an increasingly prevalent, lethal subtype of prostate cancer that arises as an adaptive
response to the application of androgen deprivation therapy and second-generation potent androgen pathway
inhibitors. Neither blood tests (such as PSA or serum neuroendocrine markers) nor standard imaging metrics
(like FDG PET) reliably distinguish NEPC from adenocarcinoma, nor quantify the degree of neuroendocrine
differentiation. The scientific premise for this proposal is based on: (i) the success of our phase 1 clinical trial of
HP 13C-pyruvate MRI in prostate cancer patients (7), (ii) the proliferation of commercially available clinical
polarizers, (iii) the technical capability to image metastatic tumors, and (iv) the strong pre-clinical data
demonstrating the value of HP 13C metabolic MRI in quantifying the MYC-mediated metabolic deregulation
associated with neuroendocrine differentiation and in measuring its response to therapy. The clinical
translation of this paradigm-shifting IGDD approach to improve the treatment of men with advanced prostate
cancer is timely and meets a new important unmet clinical need.
To accomplish this important project, we have assembled an exceptional team of basic science and clinical
investigators with complimentary expertise in pre-clinical and clinical cancer research, HP 13C MRI, and in
leading imaging and therapeutic clinical trials to: define the molecular and metabolic signature of NEPC
tumors and develop new HP 13C labeled probes to identify neuroendocrine differentiation and treatment
response (Aim 1); define the molecular and metabolic signature of metastatic NEPC tumors in patients and
correlate with HP 13C pyruvate-to-lactate flux (kPL) measurements (Aim 2); perform first-ever serial combined
HP 13C-pyruvate and HP 13C-glutamine MRI to investigate clinical value for distinguishing NEPC from
adenocarcinoma and monitoring response to treatment (Aim 3). New research on the biology of NEPC has
inspired novel investigational approaches to treating this disease, and although this proposal will focus on
current standard of care treatment, the novel quantitative HP 13C metabolic MRI approaches developed in this
proposal will have general ...

## Key facts

- **NIH application ID:** 10163810
- **Project number:** 5R01CA215694-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Rahul Aggarwal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $655,889
- **Award type:** 5
- **Project period:** 2017-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163810

## Citation

> US National Institutes of Health, RePORTER application 10163810, Targeting Neuroendocrine Prostate Cancer Using Multi-Probe Hyperpolarized 13C MRI for Improved Treatment and Therapeutic Monitoring (5R01CA215694-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10163810. Licensed CC0.

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