Abstract
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Objectives Activated microglia play a key role in inflammatory demyelinating injury in multiple sclerosis (MS). [11C]PBR28 is a PET ligand quantifying microglial activation in vivo. We evaluated the test-retest (T-RT) variability of [11C]PBR28 binding in MS patients and healthy controls (HC) with a high resolution PET.
Methods Four MS patients (relapsing-remitting type in inactive phase, age: 41±7, 2M/2F) and 4 HC (age: 42±8, 2M/2F), matched for translocator protein genotype (2 C/C and 2 C/T in each group), were studied. Dynamic data were acquired over 120 min after injection of 628±102 MBq [11C]PBR28. Subjects were scanned twice, one to three weeks apart. Brain MRIs were collected for registration, regions-of-interest analysis, partial volume correction (PVC), and MS lesion evaluation. Volume of distribution (VT) derived from MA1 modeling (t*=30 min, using arterial input data), normalized by plasma free fraction (fP) was the main outcome measure (VT/fP). PVC VT/fP was calculated in grey matter (GM). T-RT variability was evaluated. Correlation of VT/fP and clinical parameters were assessed.
Results T-RT results showed a mean absolute variation of 12±10% across GM and white matter (WM). HC VT/fP values (ml/cm3) were 258±139 in GM and 231±116 in WM; MS values were 267±76 in GM, 248±67 in WM, and 254±80 in MS lesions. No significant difference was found between lesions and normal-appearing WM of MS. VT/fP values of GM and WM in HC were higher in C/C genotype than in C/T, although it was not significant. PVC increased VT/fP by ~ 16%, with a slightly larger correction in MS. Clinical disease activity (Expanded disease status scale) was not correlated with VT/fP.
Conclusions [11C]PBR28 PET has good T-RT reproducibility for quantifying activated microglia in the human brain. Larger studies, including MS subjects from heterogeneous disease activity status, are needed to evaluate the sensitivity of this ligand.