An Open-Label Study to Investigate the Total Body Distribution and Radiation Dosimetry of the Positron Emission Tomography Ligand 18F-JNJ-64326067 in Healthy Subjects

The purpose of this study is to measure the whole-body distribution and radiation dosimetry of 18F-JNJ-64326067 in healthy participants.

开始日期2018-07-11

申办/合作机构

Janssen Research & Development LLC

NCT03239561 / Completed早期临床1期

Phase 0 Exploratory Study of [18F]MNI-1020 (Also Known as [18F]JNJ-64326067) as an Imaging Marker for Tau Protein in the Brain of Subjects With Alzheimer's Disease Compared to Healthy Subjects

The primary objectives of this study are to characterize [18F]molecular neuroimaging (MNI)-1020, a positron emission tomography (PET) radioligand for imaging tau pathology, to visually and quantitatively assess and compare brain uptake and pharmacokinetics of [18F]MNI-1020 in participants with probable Alzheimer's disease (AD) and compare with age matched healthy participants, to evaluate the safety of a single injection of [18F]MNI-1020 and to compare the distribution of tau (using [18F]MNI-1020) and amyloid beta (using florbetapir) in participants with probable AD.

开始日期2017-09-06

申办/合作机构

Janssen Research & Development LLC

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100 项与 18F-JNJ-64326067 相关的转化医学

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项与 18F-JNJ-64326067 相关的文献（医药）

2020-12-01·European Journal of Nuclear Medicine and Molecular Imaging1区 · 医学

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer’s disease

1区 · 医学

Article

作者: Rombouts, Frederik J R ; Timmers, Maarten ; Constantinescu, Cristian C ; Janssens, Luc ; Schmidt, Mark E ; Kolb, Hartmuth ; Russell, David S ; Madonia, Jennifer ; Sandiego, Christine M ; Barret, Olivier ; Moechars, Diederik

AbstractPurposeThe accumulation of misfolded tau is a common feature of several neurodegenerative disorders, with Alzheimer’s disease (AD) being the most common. Earlier we identified JNJ-64326067, a novel isoquinoline derivative with high affinity and selectivity for tau aggregates from human AD brain. We report the dosimetry of [18F] JNJ-64326067 and results of a proof-of-concept study comparing subjects with probable Alzheimer’s disease to age-matched healthy controls.Methods[18F] JNJ-64326067 PET scans were acquired for 90 min and then from 120 to 180 min in 5 participants with [18F]-florbetapir PET amyloid positive probable AD (73 ± 9 years) and 5 [18F]-florbetapir PET amyloid negative healthy controls (71 ± 7 years). Whole-body [18F] JNJ-64326067 PET CT scans were acquired in six healthy subjects for 5.5 h in 3 scanning sessions. Brain PET scans were visually reviewed. Regional quantification included kinetic analysis of distribution volume ration (DVR) estimated by Logan graphical analysis over the entire scan and static analysis of SUVr in late frames. Both methods used ventral cerebellar cortex as a reference region.ResultsOne of the healthy controls had focal areas of PET signal in occipital and parietal cortex underlying the site of a gunshot injury as an adolescent; the other four healthy subjects had no tau brain signal. Four of the 5 AD participants had visually apparent retention of [18F] JNJ-64326067 in relevant cortical regions. One of the AD subjects was visually negative. Cortical signal in visually positive subjects approached steady state by 120 min. Temporal and frontal cortical SUVr/DVR values in visually positive AD subjects ranged from 1.21 to 3.09/1.2 to 2.18 and from 0.92 to 1.28/0.91 to 1.16 in healthy controls. Whole-body effective dose was estimated to be 0.0257 mSv/MBq for females and 0.0254 mSv/MBq for males.Conclusions[18F] JNJ-64326067 could be useful for detection and quantitation of tau aggregates.

2019-03-28·Journal of Medicinal Chemistry1区 · 医学

Discovery of N-(4-[¹⁸F]Fluoro-5-methylpyridin-2-yl)isoquinolin-6-amine (JNJ-64326067), a New Promising Tau Positron Emission Tomography Imaging Tracer

1区 · 医学

Article

作者: Leenaerts, Joseph E. ; te Riele, Paula ; Iturrino, Laura ; Xia, Chunfang A. ; Song, Fengbin ; Vandenberghe, Rik ; Rombouts, Frederik J. R. ; Kolb, Hartmuth ; Andres, Jose-Ignacio ; Bormans, Guy ; Wuyts, Stijn ; Bottelbergs, Astrid ; Declercq, Lieven ; Wintmolders, Cindy ; Moechars, Diederik ; Chen, Lu ; Marien, Jonas

In Alzheimer's disease, the density and spread of aggregated tau protein track well with neurodegeneration and cognitive decline, making the imaging of aggregated tau a compelling biomarker. A structure-activity relationship exploration around an isoquinoline hit, followed by an exploration of tolerated fluorination positions, allowed us to identify 9 (JNJ-64326067), a potent and selective binder to aggregated tau with a favorable pharmacokinetic profile and no apparent off-target binding. This was confirmed in rat and monkey positron emission tomography studies using [¹⁸F]9.

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床3期	美国	Janssen Research & Development LLC	2017-09-06
诊断试剂	临床1期	-	Facultés Universitaires Catholiques de Mons	-
诊断试剂	临床1期	-	Janssen Global Services LLC	-