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Spatial Mapping of Phospholipid Biosynthesis in Brain Tumors

Award Number: R21CA286261
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Spatial Mapping of Phospholipid Biosynthesis in Brain Tumors - PROJECT SUMMARY Glioblastomas (GBMs) are malignant primary brain tumors in adults. Standard of care involves maximal safe surgical resection, radiation, and chemotherapy with temozolomide. Novel therapies are also under development for GBM patients. However, physicians are hampered in their efforts to effectively treat GBM patients by their inability to reliably monitor tumor growth in vivo. Specifically, disease progression and treatment response in GBM patients are typically monitored by non-invasive magnetic resonance imaging (MRI) methods such as contrast-enhanced MRI. However, contrast enhancement reflects the integrity of the blood brain barrier rather than any intrinsic biological activity of the tumor. As a result, it becomes difficult to reliably determine response to therapy. Tumors reprogram their metabolism to generate the biosynthetic precursors needed for proliferation. Phosphatidylcholine is the main structural component of all cellular membranes, and its biosynthesis is upregulated in most cancers due to the high membrane turnover associated with uncontrolled proliferation. The dietary nutrient choline is converted to phosphocholine (PC), which is subsequently incorporated into phosphatidylcholine. Expression of the key enzyme in this pathway, choline kinase α (CKα), is elevated in tumors relative to surrounding normal tissues, including in GBMs. Non-invasive methods of imaging CKα activity will provide the unique opportunity to visualize tumor intrinsic biological activity in vivo. Deuterium magnetic resonance spectroscopy recently emerged as an innovative clinically translatable method of imaging the metabolism of stable, non-radioactive, deuterated molecules in vivo. Our goal is to determine whether mapping CKα activity using deuterated choline enables non-invasive assessment of GBM response to therapy in vivo. We will examine the ability of deuterated choline to spatially map CKα activity (Aim 1) and provide a readout of GBM response to therapy (Aim 2) in vivo at the clinical field strength of 3T. For both aims, we will use complementary biochemical assays to confirm our DMRS data and correlate it with tumor biology. Our proposal is innovative and impactful because it will validate deuterated choline as a specific, safe, non- radioactive tracer for imaging GBM growth in vivo. By doing so, our proposal will enable precision imaging that significantly improves outcomes and quality of life for GBM patients.


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: 2026 ( Subtotal = $0 )
2026	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	2	10/7/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $226,504 )
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	2	12/9/2024	NON-COMPETING CONTINUATION	$203,853
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	001	2	6/2/2025	NON-COMPETING CONTINUATION	$22,651
														Subtotal = $226,504

Issue Date FY: 2024 ( Subtotal = $188,753 )
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	1	12/20/2023	NEW	$188,753
														Subtotal = $188,753

Grand Total All Awards = $415,257

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Spatial Mapping of Phospholipid Biosynthesis in Brain Tumors

Award Number: R21CA286261

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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