Ulrike W Kaunzner1, Yeona Kang2, Elizabeth Monohan1, Paresh J Kothari2, Nancy Nealon1, Jai Perumal1, Timothy Vartanian1, Amy Kuceyeski3, Shankar Vallabhajosula2, P David Mozley2, Claire S Riley4, Stephen M Newman5, Susan A Gauthier6. 1. Judith Jaffe Multiple Sclerosis Center, Weill Cornell Medicine, 1305 York Avenue, New York City, NY, USA. 2. Department of Radiology/Nuclear Medicine, Weill Cornell Medicine, New York, 516 E 72nd St, New York City, NY, USA. 3. Brain and Mind Research Institute, 407 East 61st street, New York City, NY, USA. 4. Multiple Sclerosis Clinical Care and Research Center, Columbia University, 710 West 168th street, New York City, NY, USA. 5. Island Neurological, 824 Old Country Road #1, Plainview, NY, USA. 6. Judith Jaffe Multiple Sclerosis Center, Weill Cornell Medicine, 1305 York Avenue, New York City, NY, USA. Electronic address: sag2015@med.cornell.edu.
Abstract
OBJECTIVE: The objective of this study is to longitudinally analyze the uptake of [11C]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.
OBJECTIVE: The objective of this study is to longitudinally analyze the uptake of [11C]PK11195-PET in multiple sclerosispatients 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.
Authors: Ulrike W Kaunzner; Yeona Kang; Shun Zhang; Eric Morris; Yihao Yao; Sneha Pandya; Sandra M Hurtado Rua; Calvin Park; Kelly M Gillen; Thanh D Nguyen; Yi Wang; David Pitt; Susan A Gauthier Journal: Brain Date: 2019-01-01 Impact factor: 13.501
Authors: Olavi Misin; Markus Matilainen; Marjo Nylund; Eveliina Honkonen; Eero Rissanen; Marcus Sucksdorff; Laura Airas Journal: Neurol Neuroimmunol Neuroinflamm Date: 2022-05-17
Authors: William C Kreisl; Min-Jeong Kim; Jennifer M Coughlin; Ioline D Henter; David R Owen; Robert B Innis Journal: Lancet Neurol Date: 2020-11 Impact factor: 44.182
Authors: Yeona Kang; David Schlyer; Ulrike W Kaunzner; Amy Kuceyeski; Paresh J Kothari; Susan A Gauthier Journal: PLoS One Date: 2018-08-09 Impact factor: 3.240
Authors: Marcus Sucksdorff; Jouni Tuisku; Markus Matilainen; Anna Vuorimaa; Sarah Smith; Joonas Keitilä; Johanna Rokka; Riitta Parkkola; Marjo Nylund; Juha Rinne; Eero Rissanen; Laura Airas Journal: Neurol Neuroimmunol Neuroinflamm Date: 2019-06-07
Authors: Colm Elliott; Jerry S Wolinsky; Stephen L Hauser; Ludwig Kappos; Frederik Barkhof; Corrado Bernasconi; Wei Wei; Shibeshih Belachew; Douglas L Arnold Journal: Mult Scler Date: 2018-12-19 Impact factor: 6.312