Journal
NUCLEAR MEDICINE COMMUNICATIONS
Volume 36, Issue 12, Pages 1239-1248Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MNM.0000000000000385
Keywords
2-amino-[3-C-11]isobutyric acid; blood-brain barrier; focused ultrasound; PET
Funding
- JSPS KAKENHI grant [24791356]
- COI Stream
- Brain/MINDS project (MEXT, Japan)
- Grants-in-Aid for Scientific Research [15K09976, 24791356] Funding Source: KAKEN
Ask authors/readers for more resources
Objective The blood-brain barrier (BBB) limits the entry of some therapeutics into the brain, resulting in reduced efficacy. BBB-opening techniques have been developed to enhance the entry into the brain. However, a noninvasive, highly sensitive and quantitative method for evaluating the changes in BBB permeability induced by such techniques is needed to optimize treatment protocols. We evaluated 2-amino-[3-C-11]isobutyric acid ([3-C-11]AIB) as a PET probe to quantify BBB permeability in model rats. Methods BBB opening was induced by a lipopolysaccharide injection or focused ultrasound (FUS) sonication. [3-C-11]AIB distribution in the brain was evaluated by autoradiography and PET and compared with that of Evans blue, a traditional BBB permeability marker. Kinetics of [3-C-11]AIB was compared with that of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI. The unidirectional blood-brain transfer constant (K-i) of [3-C-11]AIB was estimated using the Patlak plot. Results [3-C-11]AIB uptake in the lesion area was significantly higher than that in the control area and radioactivity colocalized with Evans blue in both models. [3-C-11]AIB uptake in the FUS-sonicated region decreased over time after sonication. The ratio of [3-C-11]AIB accumulation in the FUS-treated to the contralateral side increased during the experimental period, whereas that of the Gd-DTPA intensity reached a maximum at 10min after injection and decreased thereafter. The [3-C-11]AIB K-i values were significantly higher in the lesion area than the control area. Conclusion [3-C-11]AIB PET is a promising, highly sensitive and quantitative imaging method for assessment of BBB permeability. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available