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IC‐P‐187: Discovery and First‐in‐Human Evaluation of the TAU‐imaging PET Radiotracer [ 18 F]MK‐6240
Author(s) -
Bennacef Idriss,
Zeng Zhizhen,
Lohith Talakad,
Miller Patricia J.,
Salinas Cristian A.,
Connolly Brett M.,
Gantert Liza T.,
Hyking Haley D.,
Holahan Marie A.,
O’Malley Stacey S.,
Purcell Mona L.,
Riffel Kerry,
Coleman Paul J.,
Li Jing,
Balsells-Padros Jaume,
Soriano Aileen,
Ogawa Aimie M.,
Xu Serena,
Xiaoping Zhang,
Della Rocca Joseph,
Schachter Joel B.,
Hesk David,
Telan-Choing Florestina,
Struyk Arie,
Sur Cyrille,
Celen Sofie,
Serdons Kim,
Bormans Guy,
Vandenbulcke Mathieu,
Vandenberghe Rik,
De Hoon Jan,
Koole Michel,
Van Laere Koen,
Declercq Ruben,
Reynders Tom,
Abbas Walji,
Hostetler Eric D.,
Evelhoch Jeffrey
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.218
Subject(s) - radioligand , positron emission tomography , human brain , in vivo , binding potential , nuclear medicine , pittsburgh compound b , white matter , ligand (biochemistry) , pet imaging , ex vivo , chemistry , pathology , dementia , medicine , in vitro , neuroscience , magnetic resonance imaging , biology , biochemistry , receptor , disease , radiology , microbiology and biotechnology
Parametric [C]PBB3, and [C]PiB PET images were generated by calculation of target-to-cerebellar cortex standardized uptake value ratio (SUVR) at 30-50 min, and 50-70 min after radiotracer injection, respectively. [C]PiB retention was assessed by visual inspection of SUVR images. A two sample t-test was also performed on [C]PBB3 PET SUVR images between each patient and 13 HCs using SPM12. Neuropathological and autoradiographic examinations were performed in postmortem brain sections of other patients with three MAPT mutations. Results: All subjects were negative for amyloid PET. Five subjects with MAPT gene mutations exhibited increased [C]PBB3 binding in the brain compared with HCs. In the N279K mutation carriers, increased [C]PBB3 bindings were detected at an asymptomatic stage, and were spatially extended involving white matter with the progression of clinical manifestations. In contrast, patients with R406W and G272V mutations showed increased [C]PBB3 binding mostly restricted to gray matter in the brain. Autoradiographic signals and fluorescence labeling of brain sections revealed that PBB3 binds to various tau inclusions in the brain with these three mutations. Conclusions: [C]PBB3 PET can detect diverse tau inclusions, and may be useful for monitoring disease progression and therapeutic effect of anti-tau therapy in patients with MATP mutations, and other tauopathies.