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Development and Evaluation of Radiotracers for PET Imaging Angiotensin-Converting Enzyme 2 (ACE2)

Award Number: R21EB032025
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY The coronavirus disease2019 (COVID-19) pandemic is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). New COVID-19 cases and COVID-19 related deaths continue to rise rapidly and no effective drugs or vaccines are currently available. The functional entry receptor utilized by SARS-CoV-2 is Angiotensin-Converting Enzyme 2 (ACE2). SARS-CoV-2 binds to ACE2 in the lower respiratory tracts of infected patients to gain entry into lung cells, leading to viral pneumonia and potentially fatal respiratory failure. Many studies have shown that patients with comorbid conditions including respiratory disease, cardiovascular disease, kidney disease, diabetes, and hypertension have much higher mortality rates. ACE inhibitors and angiotensin receptor blockers (ARB) are frequently used to treat these pre-existing conditions and the question remains whether such treatment may affect the outcome in COVID-19 patients due to the inhibitors' effects on ACE2 expression. Many experts are concerned that those inhibitors for the treatment of patients with such underlying conditions may exacerbate COVID-19 symptoms and lead to higher mortality rates. Currently the precise relationship between ACE2 levels and severity of the infection is not well understood, due to a lack of understanding of whole-body ACE2 expression levels and distribution. Here we propose to design and synthesize a series of new fluorine-18 labeled positron emission tomography (PET) tracers targeting ACE2. The radiotracers will be evaluated in vitro for cellular binding affinity, selectivity, and metabolic stability. The most promising radiotracer will be moved to in vivo studies including whole body biodistribution with dynamic PET imaging, and correlation with biomolecular analysis in mice that express human ACE2. The PET imaging modality will provide a powerful tool for noninvasive and quantitative evaluation of ACE2 levels in living subjects. Furthermore, the radiotracer may help to unveil the precise relationship between ACE2 levels and severity of COVID-19.


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: 2023 ( Subtotal = $177,500 )
2023	2023	THE NEMOURS FOUNDATION	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	4/18/2023	NON-COMPETING CONTINUATION	$177,500
														Subtotal = $177,500

Issue Date FY: 2022 ( Subtotal = $177,500 )
2022	2022	NEMOURS FOUNDATION, THE	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	4/22/2022	NON-COMPETING CONTINUATION	$177,500
														Subtotal = $177,500

Issue Date FY: 2021 ( Subtotal = $213,000 )
2021	2021	NEMOURS FOUNDATION, THE	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	7/15/2021	NEW	$213,000
														Subtotal = $213,000

Grand Total All Awards = $568,000

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Development and Evaluation of Radiotracers for PET Imaging Angiotensin-Converting Enzyme 2 (ACE2)

Award Number: R21EB032025

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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