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Measuring Metabolic Activity in Prostate Cancer Bone Metastases Using Hyperpolarized 13C Pyruvate MRI for Improved Targeted Therapy Monitoring

Award Number: R01CA256740
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Prostate cancer is a major US health concern with over 160,000 new cases and 30,000 deaths per year. More than 90% of patients with advanced disease have bone metastases with a median survival of a year. Patients with metastatic bone disease suffer from bone pain, fractures, hypercalcemia, cytopenias, and ultimately death. The goal of this early phase “feasibility” imaging “biomarker-driven” trial is to investigate novel 3D hyperpolarized (HP) 13C-pyruvate MRI techniques to quantitatively measure lactate dehydrogenase (LDH) catalyzed pyruvate- to-lactate (kPL) conversion rates in prostate cancer bone metastases to enable early and rapid metabolic response monitoring to treatment response and development of therapeutic resistance, as well assess on-target treatment effects for new targeted drug development, thus addressing current unmet clinical needs. This clinical trial is required because current imaging modalities for bone metastases are inadequate for quantifying response to therapeutic interventions. This can result in significant delays in determining treatment effectiveness, and subjecting patients to prolonged periods of side-effects of ineffective therapies, too often causing excess morbidity without benefit. Hyperpolarized (HP) 13C-pyruvate MRI is a safe, non-radioactive, quantitative MR stable-isotope imaging approach that can provide early, real-time metabolic response monitoring of prostate cancer bone metastases. Added to conventional mpMRI exams, the rapid 2 minute HP MRI measurement of pyruvate-to-lactate conversion rate, kPL, a potentially valuable “biomarker”, reflects changes in metabolic reprogramming and early response to targeted therapies (e.g. AR, MYC inhibitors). While PSMA-PET improves detection of metastatic disease, PSMA expression is not directly affected by targeted therapies including androgen pathway inhibitors and novel MYC-targeted therapies in clinical trial evaluation, and therefore is not able to reliably capture bone metastasis response at early time points. HP 13C-pyruvate MR studies have demonstrated that MYC-mediated increased HP 13C pyruvate-to-lactate metabolic conversion rate, kPL, is associated with key oncogenomic alterations that occur with the progression to advanced prostate cancer and decreased in response to treatment. Initial studies also demonstrated that higher kPL is associated with intrinsic resistance to androgen pathway inhibitors (e.g. enzalutamide). Our multidisciplinary research team translated these findings into patient feasibility studies and performed first-ever HP 13C-pyruvate metabolic MR imaging of patients with prostate cancer bone metastases demonstrating feasibility and supporting the scientific rigor of this approach. This new biomarker- driven trial is designed to apply new HP 13C-pyruvate MRI technology for monitoring androgen-receptor and MYC targeted drug therapies with the goal of investigating kPL as a quantitative in vivo marker to measure metabolic changes with treatment in patients with bone-tropic advanced prostate cancer.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $602,753 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	5	11/5/2024	NON-COMPETING CONTINUATION	$602,753
														Subtotal = $602,753

Issue Date FY: 2024 ( Subtotal = $636,237 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	4	4/19/2024	NON-COMPETING CONTINUATION	$33,484
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	4	11/9/2023	NON-COMPETING CONTINUATION	$602,753
														Subtotal = $636,237

Issue Date FY: 2023 ( Subtotal = $656,329 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	3	3/20/2023	NON-COMPETING CONTINUATION	$53,576
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	3	11/16/2022	NON-COMPETING CONTINUATION	$602,753
														Subtotal = $656,329

Issue Date FY: 2022 ( Subtotal = $656,329 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	2	11/9/2021	NON-COMPETING CONTINUATION	$602,754
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	001	2	4/28/2022	NON-COMPETING CONTINUATION	$53,575
														Subtotal = $656,329

Issue Date FY: 2021 ( Subtotal = $669,448 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	1	11/23/2020	NEW	$669,448
														Subtotal = $669,448

Grand Total All Awards = $3,221,096

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Measuring Metabolic Activity in Prostate Cancer Bone Metastases Using Hyperpolarized 13C Pyruvate MRI for Improved Targeted Therapy Monitoring

Award Number: R01CA256740

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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