High Enantiomeric Excess In-Loop Synthesis of d-[methyl-11C]Methionine for Use as a Diagnostic Positron Emission Tomography Radiotracer in Bacterial Infection.
ACS Infect Dis
; 6(1): 43-49, 2020 01 10.
Article
em En
| MEDLINE
| ID: mdl-31697062
ABSTRACT
Currently, there exists no accurate, noninvasive clinical imaging method to detect living bacteria in vivo. Our goal is to provide a positron emission tomography (PET) method to image infection by targeting bacteria-specific metabolism. Standard of care methodologies detect morphologic changes, image immunologic response to infection, or employ invasive tissue sampling with associated patient morbidity. These strategies, however, are not specific for living bacteria and are often inadequate to detect bacterial infection during fever workup. As such, there is an unmet clinical need to identify and validate new imaging tools suitable for noninvasive, in vivo (PET) imaging of living bacteria. We have shown that d-[methyl-11C]methionine (d-[11C]Met) can distinguish active bacterial infection from sterile inflammation in a murine infection model and is sensitive to both Gram-positive and Gram-negative bacteria. Here, we report an automated and >99% enantiomeric excess (ee) synthesis of d-[11C]Met from a linear d-homocysteine precursor, a significant improvement over the previously reported synthesis utilizing a d-homocysteine thiolactone hydrochloride precursor with approximately 75-85% ee. Furthermore, we took additional steps toward applying d-[11C]Met to infected patients. d-[11C]Met was subject to a panel of clinically relevant bacterial strains and demonstrated promising sensitivity to these pathogens. Finally, we performed radiation dosimetry in a normal murine cohort to set the stage for translation to humans in the near future.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traçadores Radioativos
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Bactérias
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Infecções Bacterianas
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Tomografia por Emissão de Pósitrons
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Metionina
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
ACS Infect Dis
Ano de publicação:
2020
Tipo de documento:
Article