Reduction of PK11195 uptake observed in multiple sclerosis lesions after natalizumab initiation

Objective: The objective of this study is to longitudinally analyze the uptake of [C-11]PK11195-PET in multiple sclerosis patients after 3 and 6 months of natalizumab treatment. Methods: Eighteen MS patients, starting treatment with monocloncal anti-VLA-4, were enrolled in a longitudinal PK-PET study. PK uptake was quantified by volume of distribution (VT) calculation using image-derived input function at baseline, 3 and 6 months. Pharmacokinetic quantification was done using a segmented MRI, and selected areas included white matter, gadolinium enhancing lesions, non-enhancing lesions, cortical grey matter and thalamus. VTs of lesions were calculated in reference to each patients white matter (VT ratio = VTr), to consider physiologic variability. Results: Test-retest variability was stable for healthy control (HC). Quantification of PK uptake was completed in 18 patients, and baseline uptake was compared to 6-month uptake. After the start of natalizumab VTr significantly decreased in 13 individual enhancing lesions present within 5 patients (p = 0.001). Moreover, VTr of the sum of non-enhancing lesions showed a moderate decrease (p = 0.03). No longitudinal changes were detected in normal appearing white matter, the thalamus and cortical grey matter. Conclusion: A reduction in PK11195 uptake was observed in both enhancing and chronic lesions after the start of natalizumab. PK11195 PET can be used as tool to assess the longitudinal change in MS lesions.