Saturday, July 5, 2025 7/5/2025

Sensing living P. aeruginosa using D-alanine derived radiotracers

Award Number: R01EB030897
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: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2025

Group Awards By:

View Award Description

Sensing living P. aeruginosa using D-alanine derived radiotracers - PROJECT SUMMARY: This application addresses a major challenge that radiologists and other physicians encounter frequently, namely distinguishing active infection from other processes in the human body. Specifically, the proposed work is motivated by the difficulty in diagnosing and treating pneumonias in cystic fibrosis patients, especially those caused by P. aeruginosa. Clinically available imaging tools either (1) are limited by their background accumulation in the lungs or (2) image the host response to infection rather than the living bacteria themselves. To address this challenge, we have developed several PET radiotracers that exploit metabolic pathways specific to bacteria, including D-amino acid derived probes most recently D-[3-11C]alanine. When D-[3-11C]alanine was applied to several compelling preclinical models of infection, we found that it was exquisitely sensitive to P. aeruginosa, which is not the case for the vast majority of reported radiotracers. We further showed that D-[3-11C]alanine is a radiotracer with (1) a simple, high-yield radiosynthesis (2) good in vivo stability (3) appropriate mimicry of the endogenous substrate (4) high rate of incorporation into both gram- negative and gram-positive bacteria and (5) low uptake in background tissues. These studies demonstrate the outstanding potential of D-[3-11C]alanine, with the proposed work necessary to further validate and understand this tracer. We will first expand our radiochemical methods, synthesizing the D-[1-11C]alanine isotopomer and structurally related 18F probes (Specific Aim 1). We will then further investigate the lead 11C isotopomer in vitro, analyzing its performance in clinical P. aeruginosa strains and validated biofilm models (Specific Aim 2). In Specific Aim 3, we will extend these concepts in vivo employing both acute and chronic models of P. aeruginosa infection.


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 = $663,113 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	6/26/2024	NON-COMPETING CONTINUATION	$54,131
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	2/1/2024	NON-COMPETING CONTINUATION	$608,982
														Subtotal = $663,113

Issue Date FY: 2023 ( Subtotal = $676,646 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	1/30/2023	NON-COMPETING CONTINUATION	$676,646
														Subtotal = $676,646

Issue Date FY: 2022 ( Subtotal = $676,646 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	2/10/2022	NON-COMPETING CONTINUATION	$608,983
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	7/14/2022	NON-COMPETING CONTINUATION	$67,663
														Subtotal = $676,646

Issue Date FY: 2021 ( Subtotal = $676,646 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	4/29/2021	NEW	$676,646
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	1	5/26/2021	NEW	$0
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	1	8/30/2021	NEW	$0
														Subtotal = $676,646

Grand Total All Awards = $2,693,051

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Sensing living P. aeruginosa using D-alanine derived radiotracers

Award Number: R01EB030897

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: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer