PET Detection of Cerebral Necrosis Using an Infarct-Avid Agent 2-Deoxy-2-[18F]Fluoro-D-Glucaric Acid (FGA) in a Mouse Model of the Brain Stroke.
Mol Imaging Biol
; 22(5): 1353-1361, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32557188
PURPOSE: Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[18F]fluoro-D-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice. PROCEDURES: The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1 mice by occluding the middle cerebral artery for 1 h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with 99mTc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins. RESULTS: The kit-based synthesis was able to convert up to 2.2 GBq of FDG into FGA within 5 min. PET images showed 375 % more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55 % of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of stroke mice. CONCLUSIONS: Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Infarto Cerebral
/
Accidente Cerebrovascular
/
Tomografía de Emisión de Positrones
/
Ácido Glucárico
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Imaging Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
DIAGNOSTICO POR IMAGEM
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos