Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Development and characterization of a novel TDP-43 positron emission tomography tracer: [18F]JNJ-TDP43-1.
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Xia Chunfang A, Salarian Mani, Gartshore Christopher J, Scaglione Antonella, Hayes Thomas, Liu Shuanglong, Tsai Hsiu-Ming, Echavarren Javier, Cid Jose Maria, Matzeu Alessandra, Szardenings A Katrin
Аннотация
INTRODUCTION: Neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), limbic-predominant age-related TDP-43 encephalopathy (LATE), and Alzheimer's disease (AD) are associated with TAR DNA-binding protein 43 (TDP-43) pathology. A positron emission tomography (PET) tracer targeting TDP-43 aggregates could improve early diagnosis and guide treatment development for TDP-43-related conditions.
METHODS: Specific binding was evaluated using fluorescent labeling of compound, surface plasmon resonance (SPR), and autoradiography (ARG). Brain PET imaging in rats, nonhuman primate (NHP), and a disease mouse model was performed to characterize tracer pharmacokinetics and in vivo target binding.
RESULTS: JNJ-TDP43-1 exhibited high binding affinity for pathological TDP-43 (Kd = 7.1 nM) and remarkable selectivity over other proteinopathies. PET imaging demonstrated robust brain uptake and rapid washout in rodents and NHP. In vivo target engagement was confirmed in an AAV-hTDP43 disease model.
DISCUSSION: [18F]JNJ-TDP43-1 is a promising PET ligand for early diagnosis and evaluating therapies in TDP-43-related diseases.
METHODS: Specific binding was evaluated using fluorescent labeling of compound, surface plasmon resonance (SPR), and autoradiography (ARG). Brain PET imaging in rats, nonhuman primate (NHP), and a disease mouse model was performed to characterize tracer pharmacokinetics and in vivo target binding.
RESULTS: JNJ-TDP43-1 exhibited high binding affinity for pathological TDP-43 (Kd = 7.1 nM) and remarkable selectivity over other proteinopathies. PET imaging demonstrated robust brain uptake and rapid washout in rodents and NHP. In vivo target engagement was confirmed in an AAV-hTDP43 disease model.
DISCUSSION: [18F]JNJ-TDP43-1 is a promising PET ligand for early diagnosis and evaluating therapies in TDP-43-related diseases.