Delving into the Latest Updates on [11C]DPA-713 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

Target

TSPO

Mechanism

TSPO modulators(Translocator protein modulators), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Diagnostic agents

Originator Organization

University of Sydney Union

Active Organization-

Inactive Organization

CEA-Léti

University of Sydney Union

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H26N4O2

InChIKeyILZWUAWCTNWSFZ-SFIIULIVSA-N

CAS Registry868072-18-8

Background:
- Some people with epilepsy have an epileptic focus, a small part of the brain that is the starting point of the seizure. This focus is like an irritant or an inflammation, and helps cause the seizure. People with epilepsy that affects the temporal lobe of the brain often have an epileptic focus. Researchers want to look at the epileptic focus by using a drug that attaches to a protein associated with inflammation. An imaging study with the drug will show how much inflammation is in the area of the brain where the seizures start. The drug, called [11C]DPA-713, will be tested for its effectiveness in people with temporal lobe epilepsy. Its effects will be compared with imaging studies given to healthy volunteers.
Objectives:
- To see if [11C]DPA-713 can show the inflammation in the epileptic focus of seizures.
Eligibility:
Individuals at least 18 years of age who have temporal lobe epilepsy.
Healthy volunteers at least 18 years of age.
Design:
Participants will have three outpatient visits to the National Institutes of Health Clinical Center. The visits will last from 2 to 5 hours.
Participants will be screened with a physical exam, neurological exam, and medical history. Blood samples will be collected before the start of the study.
Participants will have a positron emission tomography (PET) scan. This scan will be used to look at brain chemistry and function. The study drug will be given during the scan to see how well it shows points of inflammation in the brain. Some participants will provide additional blood samples during the PET scan.
Participants will also have a magnetic resonance imaging (MRI) scan. This scan will look at the structure of the brain.

Start Date31 Jan 2013

Sponsor / Collaborator

National Institute of Mental Health

100 Clinical Results associated with [11C]DPA-713

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100 Translational Medicine associated with [11C]DPA-713

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100 Patents (Medical) associated with [11C]DPA-713

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11

Literatures (Medical) associated with [11C]DPA-713

01 Sep 2019·Journal of NeurologyQ2 · MEDICINE

In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease

Q2 · MEDICINE

Article

Author: Yoshikawa, Etsuji ; Higuchi, Makoto ; Ouchi, Yasuomi ; Ando, Ichiro ; Shimada, Hitoshi ; Suhara, Tetsuya ; Terada, Tatsuhiro ; Bunai, Tomoyasu ; Yokokura, Masamichi ; Obi, Tomokazu

OBJECTIVENeuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer's disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [¹¹C]PBB3 and [¹¹C]DPA713.METHODSTwenty patients with early AD and 20 age-matched normal control (NC) subjects underwent a series of PET measurements with [¹¹C]PBB3 for tau aggregation and [¹¹C]DPA713 for microglial activation (neuroinflammation). Inter- and intrasubject comparisons were performed regarding the levels of [¹¹C]PBB3 binding potential (BP_ND) and [¹¹C]DPA713 BP_ND in the light of cognitive functions using statistical parametric mapping (SPM) and regions of interest (ROIs) method.RESULTSThe [¹¹C]PBB3 BP_ND was greater in the temporo-parietal regions of AD patents than NC subjects, and a similar increasing pattern of [¹¹C]DPA713 BP_ND was observed in the same patients. Correlation analyses within the AD group showed a positive direct correlation between [¹¹C]PBB3 BP_ND and [¹¹C]DPA713 BP_ND in the parahippocampus. Pass analysis revealed that cognitive impairment was more likely linked to the level of the parahippocampal [¹¹C]PBB3 BP_ND than that of [¹¹C]DPA713 BP_ND.CONCLUSIONSThe pattern of abnormal tau deposition was very similar to that of neuroinflammation in patients with early-stage AD. Specifically, the direct positive correlation of tau pathology with neuroinflammation in the parahippocampus suggests that neuronal damage in this region is closely associated with microglial activation. Consistently, tau aggregation in this region matters more than neuroinflammation regarding the cognitive deterioration in AD.

01 Mar 2018·Journal of Neuroimmune PharmacologyQ3 · MEDICINE

The Low-Affinity Binding of Second Generation Radiotracers Targeting TSPO is Associated with a Unique Allosteric Binding Site

Q3 · MEDICINE

Article

Author: Stathis, Marigo ; Coughlin, Jennifer M ; Pomper, Martin ; Slusher, Barbara S ; Rojas, Camilo

[¹¹C]-PK11195 (PK11195) has been widely used with positron emission tomography (PET) to assess levels of the translocator protein 18 kDa (TSPO) as a marker of neuroinflammation. Recent ligands, such as [¹¹C]-PBR28 and [¹¹C]-DPA713, have improved signal-to-noise ratio and specificity for TSPO over PK11195. However, these second generation radiotracers exhibit binding differences due to a single polymorphism (rs6971) that leads to three genotypes: C/C, C/T and T/T associated with high, mixed and low binding affinities, respectively. Here we report that [³H]-DPA-713 in the presence of cholesterol or PK11195 has an accelerated dissociation rate from TSPO in platelets isolated from individuals with the T/T genotype. This allosteric interaction was not observed in platelets isolated from individuals with the C/C or C/T genotype. The results provide a molecular rationale for low binding affinity of T/T TSPO and further support the exclusion of these subjects from PET imaging studies using second generation TSPO ligands.

01 Mar 2017·Journal of Cerebral Blood Flow & MetabolismQ2 · MEDICINE

Depiction of microglial activation in aging and dementia: Positron emission tomography with [¹¹C]DPA713 versus [¹¹C](R)PK11195

Q2 · MEDICINE

Article

Author: Yokokura, Masamichi ; Iwata, Yasuhide ; Futatsubashi, Masami ; Nakaizumi, Kyoko ; Takebayashi, Kiyokazu ; Ouchi, Yasuomi ; Mori, Norio ; Terada, Tatsuhiro ; Suzuki, Katsuaki ; Yoshikawa, Etsuji ; Bunai, Tomoyasu

The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [11C]( R)PK11195 and a second-generation tracer [11C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer’s disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [11C]DPA713 BPND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [11C]( R)PK11195 BPND was used. Cognito-mnemonic scores were significantly correlated with [11C]DPA713 BPND levels in many brain regions, whereas [11C]( R)PK11195 BPND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [11C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [11C]( R)PK11195. Positron emission tomography with [11C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

100 Deals associated with [11C]DPA-713

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diagnostic agents	Phase 1	-	University of Sydney Union	-
Diagnostic agents	Phase 1	-	CEA-Léti	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SNMMI2014	Not Applicable	Epilepsy	-	[11C]DPA-713	irhpltfpwm(sbxiezlahv) = zceqqmebxi yfvksqloqr (edhokwnlmi )	-	05 Nov 2014
				[11C]PBR28[11C]DPA-713 ([11C]PBR28)	irhpltfpwm(sbxiezlahv) = osmkyvunjb yfvksqloqr (edhokwnlmi )