Authors: Anniina Snellman Johanna Rokka Francisco R LopezPicon Olli Eskola Ian Wilson Gill Farrar Mika Scheinin Olof Solin Juha O Rinne Merja HaaparantaSolin
Publish Date: 2012/07/17
Volume: 39, Issue: 11, Pages: 1784-1795
Abstract
The aim of this study was to investigate the potential of 18Fflutemetamol as a preclinical PET tracer for imaging βamyloid Aβ deposition by comparing its pharmacokinetics to those of 11CPittsburgh compound B 11CPIB in wildtype Sprague Dawley rats and C57Bl/6N mice In addition binding of 18Fflutemetamol to Aβ deposits was studied in the Tg2576 transgenic mouse model of Alzheimer’s disease18FFlutemetamol biodistribution was evaluated using ex vivo PET methods and in vivo PET imaging in wildtype rats and mice Metabolism and binding of 11CPIB and 18Fflutemetamol to plasma proteins were analysed using thinlayer chromatography and ultrafiltration methods respectively Radiation dose estimates were calculated from rat ex vivo biodistribution data The binding of 18Fflutemetamol to Aβ deposits was also studied using ex vivo and in vitro autoradiography The location of Aβ deposits in the brain was determined with thioflavine S staining and immunohistochemistryThe pharmacokinetics of 18Fflutemetamol resembled that of 11CPIB in rats and mice In vivo studies showed that both tracers readily entered the brain and were excreted via the hepatobiliary pathway in both rats and mice The metabolism of 18Fflutemetamol into radioactive metabolites was faster than that of 11CPIB 18FFlutemetamol cleared more slowly from the brain than 11CPIB particularly from white matter in line with its higher lipophilicity Effective dose estimates for 11CPIB and 18Fflutemetamol were 228 and 665 μSv/MBq respectively Autoradiographs showed 18Fflutemetamol binding to fibrillar Aβ deposits in the brain of Tg2576 miceBased on its pharmacokinetic profile 18Fflutemetamol showed potential as a PET tracer for preclinical imaging It showed good brain uptake and was bound to Aβ deposits in the brain of Tg2576 mice However its high lipophilicity might complicate the analysis of PET data particularly in smallanimal imagingThe authors wish to thank the staff of the Accelerator Laboratory for radionuclide production the staff of the Radiopharmaceutical Chemistry Laboratory for radiotracer production and Tarja Marttila Leena TokoiEklund Elisa Riuttala and Marko Vehmanen for assistance in animal studies The study was supported financially by clinical grants from Turku University Hospital project 13464 the Academy of Finland project 17652 the Sigrid Jusélius Foundation and the EU 6th Framework Project ADIT contract number 511977 which is gratefully acknowledged
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