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Intratumoral imaging of hypoxia using 1H- and 19F-MRI with redox-responsive Eu-based contrast agents

Award Number: R01EB026453
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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There is a great need for positive contrast agents for magnetic resonance imaging (MRI) that respond to levels of hypoxia in heterogeneous environments like those found in many tumors for the purpose of predicting therapeutic outcomes, developing new therapies, and enabling the testing of hypotheses relevant to our collective fundamental understanding between hypoxia and human health. Our long-term goal is to develop positive contrast agents for MRI to fill this void in diagnostic medicine by focusing on EuII-containing complexes that are among the most promising areas of study. The overall objective of this application is to establish the groundwork necessary for translation of our new 19F-EuII-based complexes into useful hypoxia-responsive contrast agents by studying the influence of the position of fluorine on ligands for europium and characterizing in vitro and in vivo indices of hypoxia. The rationale that underpins the proposed research is that EuII- containing complexes labeled with fluorine differentially (T1 or 19F) influence MRI as a function of the oxidation state of europium as we have recently demonstrated both in vitro and in vivo. The expected outcome of this proposal is the establishment of 19F-EuII-based contrast agents with defined hypoxia indices. This outcome is expected to have a positive impact by contributing to the NIH's mission in the understanding of human diseases. We plan to achieve the objective of the proposal by pursuing three specific aims: (1) to synthesize a series of redox-active Eu-based multimodal contrast agents designed rationally from our initial successful agent; (2) to characterize temperature-dependence of relaxivity and in vitro hypoxia indices for multimodal redox-active 19F-Eu-based probes for MRI; and (3) To define in vivo hypoxia indices in healthy mice, hypoxic mice, and mouse models of osteosarcoma. The new 19F-EuII-based probes will be significant because they are expected to enable changes in hypoxia resulting from therapies to be imaged, consequently aiding in assessing therapeutic efficacy and influencing the care and management of cancer patients. Furthermore, because hypoxia is relevant to a wide-range of diseases, this proposal is expected to maximize returns in many other investments of the NIH.


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 = $0 )
2024	2021	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	3/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $656,139 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	7/26/2021	NON-COMPETING CONTINUATION	$656,139
														Subtotal = $656,139

Issue Date FY: 2020 ( Subtotal = $676,601 )
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	8/14/2020	NON-COMPETING CONTINUATION	$676,601
														Subtotal = $676,601

Issue Date FY: 2019 ( Subtotal = $683,300 )
2019	2019	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	8/13/2019	NON-COMPETING CONTINUATION	$683,300
														Subtotal = $683,300

Issue Date FY: 2018 ( Subtotal = $703,151 )
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/13/2018	NEW	$703,151
														Subtotal = $703,151

Grand Total All Awards = $2,719,191

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Intratumoral imaging of hypoxia using 1H- and 19F-MRI with redox-responsive Eu-based contrast agents

Award Number: R01EB026453

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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