title: (11)C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas.
abstract: OBJECTIVE
  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 (11)C-PBR28. We evaluated the test-retest variability (TRV) and lesion detectability of (11)C-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), matched for translocator protein genotype [two high- and two medium-affinity binders according to DNA polymorphism (rs6971) in each group], were studied for TRV. 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 (11)C-PBR28. For the TRV study, subjects were scanned twice, on average 1.4 weeks apart. Volume of distribution (V T) derived from multilinear analysis (MA1) modeling (t* = 30 min, using arterial input data) 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. High-affinity binders demonstrated 30 % higher V T than medium-affinity binders in GM. Focal (11)C-PBR28 uptake was detected in two enhancing lesions of the active MS patient.
  
  
  CONCLUSIONS
  High-resolution (11)C-PBR28 PET can visualize focal areas where microglial activation is known to be present and has good test-retest reproducibility in the human brain. (11)C-PBR28 PET is likely to be valuable for monitoring both MS disease evolution and response to therapeutic strategies that target microglial activation.
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale School of Medicine, 801 Howard Avenue, PO Box 208048, New Haven, CT, 06520-8048, USA, angela.park@yale.edu.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Park
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.forename: Aracely
authors.initials: A
authors.lastname: Delgadillo
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Beata
authors.initials: B
authors.lastname: Planeta
authors.forename: Shu-Fei
authors.initials: SF
authors.lastname: Lin
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.forename: Keunpoong
authors.initials: K
authors.lastname: Lim
authors.forename: Jae-Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Anne
authors.initials: A
authors.lastname: Chastre
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Chen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Seneca
authors.forename: David
authors.initials: D
authors.lastname: Leppert
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics; D049268:Positron-Emission Tomography; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000235:genetics; D015203:Reproducibility of Results; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human
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