Wednesday, August 20, 2025 8/20/2025

Fluorescence lifetime-based tumor contrast enhancement using exogenous probes

Award Number: R01DE033427
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Fluorescence lifetime-based tumor contrast enhancement using exogenous probes - Imaging techniques that can enhance tumor contrast against non-specific background can significantly impact diagnostic and surgical applications in oncology. Fluorescence optical imaging is being evaluated for disease diagnosis and surgical treatment, using probes that either preferentially accumulate in tumors, or are antibody conjugated to label tumor-specific receptors. While there has been a significant progress in the development of molecularly targeted near infrared fluorescent probes, background fluorescence from non-specific probe accumulation remains a major confound that reduces sensitivity and specificity for tumor detection. Even when the probe clearance is rapid, tissue autofluorescence can be significant compared to the tumor fluorescence. Existing clinical optical imaging systems primarily employ fluorescence intensity-based imaging. Fluorescence intensity strongly depends on tissue attenuation and experimental factors such as excitation light intensity, and therefore cannot distinguish tumor bound probe from non-specific probe or tissue autofluorescence on an absolute scale. Our preclinical and clinical studies indicate that the fluorescence lifetimes of tumor and normal tissue in subjects injected with cancer targeted probes are distinct and independent of experimental parameters under typical conditions. We have shown that this FLT contrast dramatically improves the accuracy for tumor vs. normal classification compared to intensity-based imaging using the FDA-approved near infrared fluorescent dye, Indocyanine green (ICG). Building on this exciting finding, the goal of this proposal is to robustly validate fluorescence lifetime as a contrast mechanism for tumor identification in oral cancers using ICG. We will develop a portable time domain imaging system for concurrent intraoperative imaging and surgical specimen mapping and optimize the system using preclinical models. Subsequently, we will validate the system for intraoperative imaging and specimen margin assessment using clinical studies in head and neck cancer surgery patients systemically injected with ICG, and determine the dosage and injection time points that provide optimal accuracy for tumor vs normal classification. This proposal will also lead to future applications of lifetime contrast to enhance accuracy of tumor detection in other cancers, using ICG and novel cancer targeted probes currently under development.


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 = $450,915 )
2025	2025	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	4	8/6/2025	NON-COMPETING CONTINUATION	$450,915
														Subtotal = $450,915

Issue Date FY: 2024 ( Subtotal = $456,031 )
2024	2024	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	003	3	9/19/2024	NON-COMPETING CONTINUATION	$456,031
2024	2023	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	001	2	3/21/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$565,919
2024	2023	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	002	2	9/12/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	3/20/2024	NEW	-$565,919
														Subtotal = $456,031

Issue Date FY: 2023 ( Subtotal = $565,920 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	9/19/2023	NEW	$565,920
														Subtotal = $565,920

Grand Total All Awards = $1,472,866

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Fluorescence lifetime-based tumor contrast enhancement using exogenous probes

Award Number: R01DE033427

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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