Reduction of PK11195 uptake observed in Multiple Sclerosis Lesions after Natalizumab Initiation

Abstract Objective The objective of this study is to longitudinally analyze the uptake of [11 C]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-P...

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Published in:Multiple sclerosis and related disorders 2017-07, Vol.15, p.27-33
Main Authors: Kaunzner, Ulrike W, Kang, Yeona, Monohan, Elizabeth, Kothari, Paresh J, Nealon, Nancy, Perumal, Jai, Vartanian, Timothy, Kuceyeski, Amy, Vallabhajosula, Shankar, Mozley, P. David, Riley, Claire S, Newman, Stephen M, Gauthier, Susan A
Format: Article
Language:English
Subjects:
Adult
Antineoplastic Agents - pharmacokinetics
Female
Humans
Immunologic Factors - therapeutic use
Isoquinolines - pharmacokinetics
Lesion
Longitudinal Studies
Magnetic Resonance Imaging
Male
Microglia/Macrophages
Multiple sclerosis
Multiple Sclerosis - diagnostic imaging
Multiple Sclerosis - drug therapy
Multiple Sclerosis - metabolism
Multiple Sclerosis - pathology
Natalizumab
Natalizumab - therapeutic use
Neurology
PK11195-PET
Positron-Emission Tomography
Prospective Studies
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Summary:Abstract Objective The objective of this study is to longitudinally analyze the uptake of [11 C]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 patient's 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.
ISSN:2211-0348
2211-0356
DOI:10.1016/j.msard.2017.04.008