Work

Biological Evaluation of d -[18F]Fluoroalanine and d -[18F]Fluoroalanine-d3 as Positron Emission Tomography Imaging Tracers for Bacterial Infection

Year: 2024

Type: article

Abstract: d -Amino acids such as d -alanine are substrates for bacterial peptidoglycan biosynthesis and are selectively taken up by bacteria and not mammalian cells. Consequently, d -amino acid metabolism is an attractive target for antibiotic discovery and the development of bacteria-specific imaging agents. d -Fluoroalanine and the deuterium-labeled analogue fludalanine (MK641) were originally explored as antibiotics by Merck but failed in clinical trials due to unaccepted toxicity. Herein, we synthesized a fluorine-18 labeled d -fluoroalanine, d -3-[ 18 F]fluoroalanine ( d -[ 18 F]FAla), and its deuterated analogue, d -3-[ 18 F]fluoroalanine- d 3 ( d -[ 18 F]FAla- d 3 ), and evaluated their capability to image bacterial infection. Both d -[ 18 F]FAla and d -[ 18 F]FAla- d 3 can accumulate up to 0.64–0.78% ID/cc in the infectious area at 15 min postinjection. Despite the reduction of in vivo defluorination not being observed for deuterated 18 F-labeled d -fluoroalanine, these radiolabeled d -alanine analogues were able to differentiate bacterial infection from sterile inflammation in a soft-tissue model of S. aureus infection.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/acs.jmedchem.4c00783