Delving into the Latest Updates on 11C-PE2I with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

Target

DAT

Mechanism

DAT antagonists(Dopamine transporter antagonists), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Parkinson Disease

Inactive Indication-

Originator Organization

Karolinska University Hospital

Active Organization

Uppsala University Hospital

Inactive Organization

Karolinska University Hospital

Drug Highest PhaseClinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC19H24INO2

InChIKeyYYCOWMQMXNLRHZ-JCEKTBGXSA-N

CAS Registry311767-40-5

Prospective, single center study to determine whether the current R2* iron mapping method for measuring nigral iron changes in the brain can be significantly improved by using the Quantitative Susceptibility Mapping (QSM) based iron mapping techniques with the goal of validating QSM for potential use in later clinical trials. Subjects with a diagnosis of Parkinson's Disease, Rapid Eye Movement (REM) Sleep Behavior Disorder, and Normal Volunteers who meet the inclusion and exclusion criteria will be eligible for participation in this study.

Start Date14 Aug 2018

Sponsor / Collaborator

Weill Medical College of Cornell University

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100 Clinical Results associated with 11C-PE2I

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100 Translational Medicine associated with 11C-PE2I

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100 Patents (Medical) associated with 11C-PE2I

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17

Literatures (Medical) associated with 11C-PE2I

23 May 2023·EJNMMI research

Sertraline treatment influences [¹⁸F]FE-PE2I PET imaging for Parkinsonism.

Article

Author: Hovind, Peter ; Borghammer, Per ; Aanerud, Joel ; Marner, Lisbeth ; Justesen, Thomas E H

BACKGROUNDThe dopamine transporter (DaT) PET ligand [¹⁸F]FE-PE2I is used to aid the diagnosis of Parkinson's disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [¹⁸F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [¹⁸F]FE-PE2I binding due to sertraline's high affinity for DaT.METHODSWe rescanned the four patients with [¹⁸F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson's, were used to estimate the effect on tracer binding. Comparison was made to a patient with [¹⁸F]FE-PE2I PET before and after a 7-day Modafinil pause.RESULTSWe found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline.CONCLUSIONSertraline is one of the most commonly used antidepressants and in contrast to other SSRI's, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [¹⁸F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day.

01 May 2011·Danish medical bulletin

Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT.

Review

Author: Ziebell, Morten

Imaging of the dopamine transporter (DAT) with Single Photon Emission Computer Tomography (SPECT) has increasingly been used as a biomarker for the integrity of presynaptic dopaminergic nerve cells in patients with movement disorders. 123-I-labelled N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane, named PE2I, is a relatively new radioligand that has about 10-fold higher in vitro selectivity for the DAT than for the serotonin transporter (SERT) compared to the slightly older but very used and licensed radioligand [123I]FP-CIT (DaTSCAN). Further [123I]PE2I has faster kinetics than [123I]FP-CIT. Because of its fast kinetic properties, quantification of [123I]PE2I binding to DAT is possible using kinetic or graphical analysis following bolus injection of tracer or as a combination of bolus and constant infusion. Based on preliminary bolus trials we have been able to calculate a B/I ratio of [123I]PE2I. This B/I ratio (2.7h) gave rise to steady state conditions and excellent reproducibility. Further, manual delineation of ROI directly on SPECT images performed equally well to a MRI-defined probability map based ROI delineation in terms of intrasubject variability of binding potential of DAT. Finally the in vivo SERT binding in DAT images obtained with [123I]FP-CIT was significant as compared to the [123I]PE2I image. [123I]PE2I is a super selective SPECT DAT radioligand with optimal kinetic properties for accurate quantification of the DAT availability in striatum. Apart from the more laborious B/I design it is currently to be considered the best radioligand for imaging the DAT in the human brain with SPECT.

01 Mar 2011·Journal of Nuclear MedicineQ1 · MEDICINE

Transport of Selected PET Radiotracers by Human P-Glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2): An In Vitro Screening

Q1 · MEDICINE

Article

Author: Scherrmann, Jean-Michel ; Kuhnast, Bertrand ; Goutal, Sebastien ; Bottlaender, Michel ; Dolle, Frederic ; Tournier, Nicolas ; Cisternino, Salvatore ; Valette, Heric ; Saba, Wadad ; Peyronneau, Marie-Anne

Radiolabeled compounds used for brain imaging with PET must readily cross the blood-brain barrier (BBB) to reach their target. Efflux transporters at the BBB-P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP)-could limit their uptake by the brain.METHODSWe developed and validated an in vitro model using MDCKII cells transfected with human multidrug resistance (MDR1) or BCRP genes and assessed the transport of selected PET ligands by the concentration equilibrium technique. The tested compounds included befloxatone, (R,S)-CGP-12177, clorgyline, R-(-)-deprenyl, diprenorphine, DPA-714, fallypride, flumazenil, 2-fluoro-A-85380, LBT-999, loperamide, p-MPPF, PE2I, Pittsburgh compound B (PIB), (R,S)-PK11195, raclopride, R-(+)-verapamil, and WAY-100635. The assays were performed using the nonradioactive form of each compound (ultraviolet high-performance liquid chromatography analysis) and, when available, the (18)F-labeled analogs (γ-counting).RESULTSBefloxatone appeared to be transported solely by BCRP. Loperamide, verapamil, and diprenorphine were the only P-gp substrates. Other ligands were transported by neither P-gp nor BCRP.CONCLUSIONThe present method can readily be used to screen new-compound transport by P-gp or BCRP, even before any radiolabeling. Compounds that were previously thought to be transported by P-gp in rodents, such as p-MPPF, WAY-100635, and flumazenil, cannot be considered substrates of human P-gp. The impact of BCRP and P-gp at the BBB on the transport of befloxatone and diprenorphine in vivo remains to be evaluated with PET.

100 Deals associated with 11C-PE2I

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 1	SE	Karolinska University Hospital	03 Jun 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SNMMI2023	Not Applicable	Parkinson Disease	-	11C-PE2I (Parkinson’s disease patients)	xtuiukytef(mmnqlfulsz) = ntqauooyzd cpehmzwnzd (tkpxlwyuhy, 8.78) View more	-	28 Aug 2023
				11C-PE2I (Healthy controls)	xtuiukytef(mmnqlfulsz) = urptzgbhxs cpehmzwnzd (tkpxlwyuhy, 4.95) View more