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

Authors: Zhisheng Jia; Martin Bolin; Anton Forsberg Morén; Prodip Datta; Heba Asem; Hans Ågren; Bengt Långström; +3 Authors

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

Abstract

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 [11C]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 [11C]KIn83 using non-human primate (NHP) whole-body PET data. Radiolabeling and drug product delivery of [11C]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 [11C]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 [11C]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 [11C]KIn83 to measure α7-nAChR, aiding our understanding and possibly supporting diagnoses of different cognitive disorders.

Keywords

Radiology and Medical Imaging, dosimetry, alpha7 Nicotinic Acetylcholine Receptor, Neurosciences, Organic chemistry, non-human primate, Alzheimer's disease, Article, Macaca fascicularis, PET, QD241-441, Positron-Emission Tomography, Animals, Humans, Female, Radiologi och bildbehandling, Carbon Radioisotopes, nicotinic acetylcholine receptor, Radiopharmaceuticals, Radiometry, Alzheimer’s disease, Neurovetenskaper

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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