Good Manufacturing Practice Validation and Radiation Dosimetry for the Clinical Application of a Novel α7-nAChR Radioligand: [<sup>11</sup>C]KIn83

Nicotinic acetylcholine receptor (α7-nAChR) plays a crucial role in cognitive functions like memory and attention. Positron emission tomography (PET) imaging of α7-nAChR is gaining attraction for understanding and monitoring central nervous system disorders, such as Alzheimer’s disease, Parkinson’s...

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Main Authors: Zhisheng Jia, Martin Bolin, Anton Forsberg Morén, Prodip Datta, Heba Asem, Hans Ågren, Bengt Långström, Agneta Nordberg, Christer Halldin, Sangram Nag
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/6/1356
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Summary:Nicotinic acetylcholine receptor (α7-nAChR) plays a crucial role in cognitive functions like memory and attention. Positron emission tomography (PET) imaging of α7-nAChR is gaining attraction for understanding and monitoring central nervous system disorders, such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia. We developed [<sup>11</sup>C]KIn83, a novel α7-nAChR radioligand, and evaluated its biological properties. This study focused on two objectives: (1) to validate its Good Manufacturing Practice (GMP)-compliant production, and (2) to assess the dosimetry of [<sup>11</sup>C]KIn83 using non-human primate (NHP) whole-body PET data. Radiolabeling and drug product delivery of [<sup>11</sup>C]KIn83 were conducted using an automated synthesis module within a controlled GMP environment. The quality control tests performed adhered to the European Pharmacopoeia guidelines. The production of [<sup>11</sup>C]KIn83 was validated according to GMP standards, encompassing automated synthesis and quality control measures. For the dosimetry assessment, two female cynomolgus monkeys underwent whole-body PET scans. The radioactivity values injected for [<sup>11</sup>C]KIn83 were 150 MBq and 155 MBq, respectively, with an estimated radiation dose of 0.0047 mSv/MBq. Our findings pave the way for future clinical studies that investigate the potential of [<sup>11</sup>C]KIn83 to measure α7-nAChR, aiding our understanding and possibly supporting diagnoses of different cognitive disorders.
ISSN:1420-3049