Quantitative tracking of inflammatory activity at the peak and trough plasma levels of tofacitinib, a Janus kinase inhibitor, via in vivo 18 F-FDG PET

• Published in: International journal of rheumatic diseases Vol. 22; no. 12; pp. 2165 - 2169
• Main Authors: Raychaudhuri, Sanchita, Abria, Christine, Harmany, Zachary T, Smith, Charles M, Kundu-Raychaudhuri, Smriti, Raychaudhuri, Siba P, Chaudhari, Abhijit J
• Format: Journal Article
• Language: English
• Published: England 01.12.2019
• Subjects: Animals; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - blood; Antirheumatic Agents - pharmacokinetics; Arthritis, Experimental - blood; Arthritis, Experimental - diagnostic imaging; Arthritis, Experimental - drug therapy; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - drug therapy; Drug Administration Schedule; Fluorodeoxyglucose F18 - administration & dosage; Janus Kinase Inhibitors - administration & dosage; Janus Kinase Inhibitors - blood; Janus Kinase Inhibitors - pharmacokinetics; Joints - diagnostic imaging; Joints - drug effects; Male; Mice, Inbred DBA; Piperidines - administration & dosage; Piperidines - blood; Positron-Emission Tomography; Predictive Value of Tests; Pyrimidines - administration & dosage; Pyrimidines - blood; Pyrroles - administration & dosage; Pyrroles - blood; Radiopharmaceuticals - administration & dosage; Whole Body Imaging; collagen-induced arthritis; joint inflammation; 18F-FDG; positron emission tomography; Janus kinase inhibitor; tofacitinib
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.13732

To assess the capability of in vivo positron emission tomography (PET) using F-fluorodeoxyglucose ( F-FDG) to quantify changes in inflammatory activity in response to tofacitinib, a Janus kinase (JAK) inhibitor, over a timeframe of a few hours to few days in a preclinical model of rheumatoid arthritis (RA). Twenty-four mice with collagen-induced arthritis in the following groups were assessed: Group 1, where the changes in PET measures for the extremity joints were evaluated at the peak and trough plasma drug levels after administration of a single dose of tofacitinib (4 hours apart); Group 2, where joint PET measures were assessed before treatment and after 6 days of administration of a daily dose of tofacitinib; and group 3 (controls), where joint PET measures were derived from the same mice, 6 days apart. At about peak plasma levels of the drug after a single tofacitinib administration, there was a reduction in PET measures compared to pretreatment values, suggesting decreased inflammatory activity. These measures were equivalent to those obtained after 6 days of daily dosing by tofacitinib. However, PET measures at trough plasma levels of the drug from tofacitinib administration were significantly higher than those at peak plasma drug levels and equivalent to pretreatment measures. There were insignificant changes in PET measures for the control animals. F-FDG PET can detect changes in inflammatory activity occurring in response to the JAK inhibitor tofacitinib: (a) during peak and trough plasma drug levels, that is within mere hours of treatment; and (b) over a span of days.