Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027121 (
myositis
)
4,538
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Incorporation of d-amino acids into peptidoglycan is a unique metabolic feature of bacteria. Since d-amino acids are not metabolic substrates in most mammalian tissues, this difference can be exploited to detect living bacteria
in vivo
. Given the prevalence of d-alanine in peptidoglycan muropeptides, as well as its role in several antibiotic mechanisms, we targeted this amino acid for positron emission tomography (PET) radiotracer development. d-[3-
11
C]
Alanine
and the dipeptide d-[3-
11
C]alanyl-d-alanine were synthesized via asymmetric alkylation of glycine-derived Schiff-base precursors with [
11
C]methyl iodide in the presence of a cinchonidinium phase-transfer catalyst. In cell experiments, both tracers showed accumulation by a wide variety of both Gram-positive and Gram-negative pathogens including
Staphylococcus aureus
and
Pseudomonas aeruginosa
. In a mouse model of acute bacterial
myositis
, d-[3-
11
C]alanine was accumulated by living microorganisms but was not taken up in areas of sterile inflammation. When compared to existing clinical nuclear imaging tools, specifically 2-deoxy-2-[
18
F]fluoro-d-glucose and a gallium citrate radiotracer, d-alanine showed more bacteria-specific uptake. Decreased d-[3-
11
C]alanine uptake was also observed in antibiotic-sensitive microbes after antimicrobial therapy, when compared to that in resistant organisms. Finally, prominent uptake of d-[3-
11
C]alanine uptake was seen in rodent models of discitis-osteomyelitis and
P. aeruginosa
pneumonia. These data provide strong justification for clinical translation of d-[3-
11
C]alanine to address a number of important human infections.
...
PMID:Sensing Living Bacteria
in Vivo
Using d-Alanine-Derived
11
C Radiotracers. 3212 33
