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Preclinical evaluation of a microtubule PET ligand [C-11]MPC-6827 in tau and amyotrophic lateral sclerosis animal models

Kumar, JS Dileep; Molotkov, Andrei; Kim, Jongho; Carberry, Patrick; Idumonyi, Sidney; Castrillon, John; Duff, Karen; ... Mintz, Akiva; + view all (2022) Preclinical evaluation of a microtubule PET ligand [C-11]MPC-6827 in tau and amyotrophic lateral sclerosis animal models. Pharmacological Reports , 74 pp. 539-544. 10.1007/s43440-022-00359-y. Green open access

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Abstract

Background: Microtubules are abundant in brain and their malfunctioning occurs in the early-to-advanced stages of neurodegenerative disorders. At present, there is no in vivo test available for a definitive diagnosis of most of the neurodegenerative disorders. Herein, we present the microPET imaging of microtubules using our recently reported Positron Emission Tomography (PET) tracer, [11C]MPC-6827, in transgenic mice models of tau pathology (rTg4510) and amyotrophic lateral sclerosis pathology (SOD1*G93A) and compared to corresponding age-matched controls. / Methods: Automated synthesis of [11C]MPC-6827 was achieved in a GE-FX2MeI/FX2M radiochemistry module. In vivo PET imaging studies of [11C]MPC-6827 (3.7 ± 0.8 MBq) were performed in rTg4510 and SOD1*G93A mice groups and their corresponding littermates (n = 5 per group). Dynamic PET images were acquired using a microPET Inveon system (Siemens, Germany) at 55 min for rTg4510 and 30 min for SOD1*G93A and corresponding controls. PET images were reconstructed using the 3D-OSEM algorithm and analyzed using VivoQuant version 4 (Invicro, MA). Tracer uptake in ROIs that included whole brain was measured as %ID/g over time to generate standardized uptake values (SUV) and time–activity curves (TACs). / Results: [11C]MPC-6827 exhibit a trend of lower tracer binding in mouse models of Alzheimer’s disease (tau pathology, line rTg4510) and Amyotrophic Lateral Sclerosis (line SOD1*G93A) compared to wild-type littermates. / Conclusions: Our finding indicates a trend of loss of microtubule binding of [11C]MPC-6827 in the whole brain of AD and ALS transgenic mice models compared to control mice. The pilot studies described herein show that [11C]MPC-6827 could be used as a PET ligand for preclinical and human brain imaging of Alzheimer’s disease, ALS, and other neurodegenerative diseases. Graphical abstract: Preclinical Evaluation of a Microtubule PET Ligand [11C]MPC-6827 in Tau and Amyotrophic Lateral Sclerosis Animal Models. J. S. Dileep Kumar, Andrei Molotkov, Jongho Kim, Patrick Carberry, Sidney Idumonyi, John Castrillon, Karen Duff, Neil A. Shneider, Akiva Mintz [Figure not available: see fulltext.].

Type: Article
Title: Preclinical evaluation of a microtubule PET ligand [C-11]MPC-6827 in tau and amyotrophic lateral sclerosis animal models
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s43440-022-00359-y
Publisher version: http://doi.org/10.1007/s43440-022-00359-y
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Microtubule, PET, Alzheimer's disease, Amyotrophic lateral sclerosis
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/10148167
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