Sunday, 5 April 2015

Imaging Hot Microglia

Park E, Gallezot JD, Delgadillo A, Liu S, Planeta B, Lin SF, O'Connor KC, Lim K, Lee JY, Chastre A, Chen MK, Seneca N, Leppert D, Huang Y, Carson RE, Pelletier D. PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas.
Eur J Nucl Med Mol Imaging. 2015 Apr 2. [Epub ahead of print]

PURPOSE:Activated microglia play a key role in inflammatory demyelinating injury in multiple sclerosis (MS). Microglial activation can be measured in vivo using a positron emission tomography (PET) ligand 11C-PBR28. We evaluated the test-retest variability (TRV) and lesion detectability of 11C-PBR28 binding in MS subjects and healthy controls (HCs) with high-resolution PET.
METHODS: Four clinically and radiologically stable relapsing-remitting MS subjects (age 41 ± 7 years, two men/two women) and four HCs (age 42 ± 8 years, 2 two men/two women). Another MS subject (age 41 years, male) with clinical and radiological activity was studied for lesion detectability. Dynamic data were acquired over 120 min after injection of 634 ± 101 MBq 11C-PBR28. For the TRV study, subjects were scanned twice, on average 1.4 weeks apart. Volume of distribution (V T) was the main outcome measure.
RESULTS: Mean test V T values (ml cm-3) were 3.9 ± 1.4 in the whole brain gray matter (GM), 3.6 ± 1.2 in the whole brain white matter (WM) or normal-appearing white matter (NAWM), and 3.3 ± 0.6 in MS WM lesions; mean retest V T values were 3.7 ± 1.0 in GM, 3.3 ± 0.9 in WM/NAWM, and 3.3 ± 0.7 in MS lesions. Test-retest results showed a mean absolute TRV ranging from 7 to 9 % across GM, WM/NAWM, and MS lesions.  Focal 11C-PBR28 uptake was detected in two enhancing lesions of the active MS patient.
CONCLUSION: High-resolution 11C-PBR28 PET can visualize focal areas where microglial activation is known to be present and has good test-retest reproducibility in the human brain. 11C-PBR28 PET is likely to be valuable for monitoring both MS disease evolution and response to therapeutic strategies that target microglial activation.

PBR28 is a molecule that binds to benzodiazipine receptors, which are found on microglia. In this study thy make PBR28 radioactive. Carbon has a molecular weight of 12, it contains six protons, six neutrons and six electrons and you may have heard of Carbon 14 which is a radioactive isotope of carbon with a nucleus containing 6 protons and 8 neutrons. Its presence in organic materials is the basis of the radiocarbon dating The half-life of carbon-14 is 5,730±40 years meaning that the amount halves about every 6000 years. In contrast, Carbon-11 which is commonly used as a radioisotope for the radioactive labeling of molecules in positron emission tomography has a half-life of 20 minutes. So it disapppears quickly. In this study the added C-11 to PBR28 and did imaging and repeated this with good correlation. This could be a rapid way to find inhibitors of hot microglia.

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