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Cherenkov luminescence mediated excitation of discrete lanthanide optical probes

Award Number: R21EB030071
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: 08/23/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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Cherenkov luminescence mediated excitation of discrete lanthanide optical probes - Precision medicine requires tools that visualize diseased cells to enable diagnosis, facilitate surgical resection, and monitor therapeutic response. Technologies to identify the interface of cancer and healthy tissues require the ability to illuminate cancer cells with exceptional selectivity over healthy cells. This also requires optical imaging probes that can selectively illuminate cancer in vivo. To date, molecular optical dyes utilized for preclinical and clinical imaging studies are comprised of lipophilic organic molecules with limited water solubility, predominantly hepatic clearance profile, residing in an “always on” state. These significant drawbacks motivate investigation of alternative optical probes that exhibit improved water solubility and pharmacokinetics paired with the ability to produce signal only in the target tissues of interest. Luminescent lanthanide complexes with emissive properties in the first NIR (near-infrared) window provide a highly water soluble and biocompatible alternative to lipophilic organic fluorophores with predominantly hepatic clearance profiles. Excitation of luminescent lanthanides is most efficient at wavelengths of 250–350 nm. While the resulting, effective Stokes-shift of is conveniently large, the short-wavelength excitation is incompatible with the first biological optical imaging window of 550–1000 nm. This has prevented application of discrete luminescent lanthanide complexes as optical probes for in vivo imaging applications to date. Our group has pioneered the application of Cherenkov radiation (CR) of radionuclides for the in situ excitation of discrete lanthanide complexes. CR is produced by isotopes decaying under emission of charged particles in dielectric media and exhibits a maximum intensity below 400 nm. We have demonstrated that luminescent lanthanide antenna complexes are ideal acceptors for Cherenkov radiation-mediated energy transfer (CRET). Here, we propose to devise and implement targeted CRET lanthanide probes to image cancer heterogeneity with multiplexed, optical imaging in vivo.


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: 2024 ( Subtotal = $187,715 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	4	5/27/2024	NON-COMPETING CONTINUATION	$18,771
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	12/15/2023	NON-COMPETING CONTINUATION	$168,944
2024	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	3	5/21/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$31,963
2024	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	5/21/2024	NON-COMPETING CONTINUATION	-$31,963
														Subtotal = $187,715

Issue Date FY: 2023 ( Subtotal = $186,662 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	3	8/23/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$142,175
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	2	8/22/2023	NON-COMPETING CONTINUATION	-$151,525
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	1/24/2023	NON-COMPETING CONTINUATION	$19,601
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	12/12/2022	NON-COMPETING CONTINUATION	$176,411
														Subtotal = $186,662

Issue Date FY: 2021 ( Subtotal = $235,887 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	1	5/26/2021	NEW	$0
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	3/31/2021	NEW	$235,887
														Subtotal = $235,887

Grand Total All Awards = $610,264

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Cherenkov luminescence mediated excitation of discrete lanthanide optical probes

Award Number: R21EB030071

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: 08/23/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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