Sunday, March 15, 2026 3/15/2026

Interleaved 1H/23Na imaging for invasive and proliferative phenotypes of brain tumors

Award Number: R01CA280871
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/08/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Interleaved 1H/23Na imaging for invasive and proliferative phenotypes of brain tumors - Invasive and proliferative phenotypes are vital cancer hallmarks, and these phenotypes are distinguished by the fact that invasive cells lead the path for dividing cells as the tumor grows. Glioblastoma multiforme (GBM) treatments, specifically chemotherapies, fail because cancer cells invade and proliferate beyond tumor boundaries. But neither phenotypes can be tracked with existing imaging methods. We will develop 1H/23Na MRSI technology to differentiate and track these phenotypes, and which will have major clinical relevance. Compared to normal cells, cancer cells possess unique chemical and electrical properties. Interstitial fluid's acidity and salinity are crucial for cell survival. Many cellular mechanisms help regulate essential cellular functions by maintaining hydrogen ions (H+) and sodium ions (Na+) in the interstitial milieu, which is saline and near neutral pH. Research from us, and others, reveal that acidity and salinity of interstitial and intracellular spaces are altered in cancer, e.g., sodium-hydrogen exchanger 1 (NHE1), which aids H+ efflux and Na+ influx, is upregulated in GBMs and contributes to altered transmembrane ion distributions. Research on GBM models reveals an acidic interstitial fluid, vital for reshaping the interstitial matrix for cancer cell proliferation and to guide cancer cell invasion. Similar work on human-derived GBMs shows that interstitial Na+ is also altered, but this change supports a depolarized cell membrane - vital for cancer cell proliferation. These novel results suggest that the combination of interstitial pH (pHo) and transmembrane Na+ gradient (ΔNa+m) maps can help generate independent biomarkers of invasive and proliferative phenotypes. While 1H-MRI with gadolinium agents tracks tumor size, we and others have shown that agents with other lanthanides can be used for pHo mapping with 1H-MRSI and ΔNa+m mapping with 23Na-MRSI. These 1H/23Na maps are currently obtained individually, requiring lengthy acquisitions with separate agent injections. To explore the relationship between dysregulated pH and electrolyte imbalances regulating cancer cell invasion and proliferation, pHo and ΔNa+m maps must be spatiotemporally compared during tumor growth/therapy. Our goal is to test the hypothesis that invasive cells lead dividing cells as the tumor grows, and explore how their patterns change with treatment. First, we will interleave 1H and 23Na acquisitions to enable rapid pHo and ΔNa+m mapping with a single agent infusion. Next, proliferative and invasive maps from combination of pHo and ΔNa+m maps will be validated in nodular vs. invasive patient -derived xenografts (PDXs) using IHC and ICP-MS. For clinical relevance, we will test potential of NHE1 inhibitor as an adjuvant chemotherapy to improve GBM outcome. We will compare pHo and ΔNa+m maps with two different therapies (i.e., first-line GBM standard of care chemotherapy temozolomide alone vs. temozolomide + cariporide) to capture fates of invasive and proliferative phenotypes in nodular vs. invasive PDXs.


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 = $565,665 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Detection and Diagnosis Research	000	4	3/2/2026	NON-COMPETING CONTINUATION	$565,665
														Subtotal = $565,665

Issue Date FY: 2025 ( Subtotal = $564,399 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Detection and Diagnosis Research	000	3	3/3/2025	NON-COMPETING CONTINUATION	$507,961
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Detection and Diagnosis Research	001	3	5/22/2025	NON-COMPETING CONTINUATION	$56,438
														Subtotal = $564,399

Issue Date FY: 2024 ( Subtotal = $535,021 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Detection and Diagnosis Research	001	2	4/17/2024	NON-COMPETING CONTINUATION	$28,158
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Detection and Diagnosis Research	000	2	2/7/2024	NON-COMPETING CONTINUATION	$506,863
														Subtotal = $535,021

Issue Date FY: 2023 ( Subtotal = $572,851 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Detection and Diagnosis Research	000	1	3/8/2023	NEW	$572,851
														Subtotal = $572,851

Grand Total All Awards = $2,237,936

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Interleaved 1H/23Na imaging for invasive and proliferative phenotypes of brain tumors

Award Number: R01CA280871

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/08/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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