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Biocompatible fluorophores for shortwave infrared imaging

Award Number: R01EB027172
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/13/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Biocompatible fluorophores for shortwave infrared imaging - The shortwave infrared (SWIR) region of the electromagnetic spectrum has become an exciting avenue for imaging in mammals due to the increased penetration of light through tissue, decreased light scattering, and minimal autofluorescence. In the previous granting period, we showcased an additional advantage of the SWIR region– the enhanced spectral real estate which facilitates non-invasive multicolor imaging in mice. Taken together, all these advantages set the stage for: 1) fundamental biological studies in animal models analogous to those which have been enormously successful in cells and transparent organisms, 2) the ability to evaluate controls in same animal as the experimental group, and 3) advanced clinical diagnostics for both intraoperative and non-invasive use. While the SWIR region has great potential, it cannot be realized without biocompatible contrast agents. This proposal focuses on contrast agent development for high resolution multicolor imaging in the SWIR region, building on the expertise we have gained in polymethine fluorophores over the last granting period. We have prepared over 100 polymethine fluorophores and gained predictive metrics on the most classical photophysical parameters of lmax.abs, lmax,em and FF. We have also learned some key lessons regarding utility of the fluorophores including how to solubilize them in water and have gained appreciation for the different approaches to formulating fluorophores for imaging. In collaboration with the Bruns laboratory, we demonstrated excitation-based multicolor imaging with fluorophores well-matched to common laser lines. In the next granting period, we specifically focus on optimizing fluorophores for use in excitation-based multiplexing with detection in the high-resolution region of the SWIR (above 1400 nm) such that mm resolution can be achieved. Aim 1 explores the chromophore scaffold itself optimizing the photophysical properties for maximum absorption at commercial laser lines and emission >1400 nm. We take a physical organic chemistry approach to fluorophore optimization and capitalize on the continually growing, fully characterized set of systematically modified fluorophores our laboratory has prepared. Our work is aided by computation and theory collaborations with the Lopez and Caram Laboratories. Aim 2 transforms the lead fluorophores from aim 1 into water-soluble, targeted contrast agents. Finally in Aim 3, we aim image the lymphatic system, demonstrating the need for mm resolution imaging and then using excitation-based multicolor imaging to evaluate sentinel lymph node mapping and cancer metastasis.


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 = $0 )
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	6	4/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $374,481 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	6	8/22/2024	NON-COMPETING CONTINUATION	$374,481
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	5	8/6/2024	COMPETING CONTINUATION	$251,717
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	11/1/2023	COMPETING CONTINUATION	$0
2024	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	8/6/2024	NON-COMPETING CONTINUATION	-$251,717
														Subtotal = $374,481

Issue Date FY: 2023 ( Subtotal = $382,124 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	5	9/12/2023	COMPETING CONTINUATION	$382,124
2023	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	9/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $382,124

Issue Date FY: 2022 ( Subtotal = $342,698 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	12/14/2021	NON-COMPETING CONTINUATION	$308,428
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	6/29/2022	NON-COMPETING CONTINUATION	$34,270
														Subtotal = $342,698

Issue Date FY: 2021 ( Subtotal = $335,844 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	12/22/2020	NON-COMPETING CONTINUATION	$308,428
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	6/2/2021	NON-COMPETING CONTINUATION	$27,416
														Subtotal = $335,844

Issue Date FY: 2020 ( Subtotal = $342,698 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	1/14/2020	NON-COMPETING CONTINUATION	$342,698
														Subtotal = $342,698

Issue Date FY: 2019 ( Subtotal = $322,538 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	2/1/2019	NEW	$322,538
														Subtotal = $322,538

Grand Total All Awards = $2,100,383

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Biocompatible fluorophores for shortwave infrared imaging

Award Number: R01EB027172

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/13/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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