Delving into the Latest Updates on Florbenazine F18 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

(+)-18FP-DTBZ, 18F-FP-Dihydrotatetrabenazine, [18F]FP-(+)- DTBZ

+ [7]

Target

VMAT2

Mechanism

VMAT2 inhibitors(Synaptic vesicular amine transporter inhibitors), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseOther Diseases+ [1]

Active Indication-

Inactive Indication

Alzheimer DiseaseDiabetes Mellitus, Insulin-Dependent, 2Diabetes Mellitus, Type 2+ [6]

Originator Organization

University of Michigan College of Engineering

Active Organization-

Inactive Organization

Avid Radiopharmaceuticals, Inc.Chang Gung Memorial Hospital

Drug Highest PhaseDiscontinuedPhase 2/3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H32FNO3

InChIKeyGNKGXQHHUUEYQV-WTHAECTESA-N

CAS Registry956903-29-0

PURPOSEA unique advantage of the brain positron emission tomography (PET) imaging is the ability to image different biological processes with different radiotracers. However, the diversity of the brain PET image patterns also makes their spatial normalization challenging. Since structural MR images are not always available in the clinical practice, this study proposed a PET-only spatial normalization method based on adaptive probabilistic brain atlas.METHODSThe proposed method (atlas-based method) consists of two parts, an adaptive probabilistic brain atlas generation algorithm, and a probabilistic framework for registering PET image to the generated atlas. To validate this method, the results of MRI-based method and template-based method (a widely used PET-only method) were treated as the gold standard and control, respectively. A total of 286 brain PET images, including seven radiotracers (FDG, PIB, FBB, AV-45, AV-1451, AV-133, [¹⁸F]altanserin) and four groups of subjects (Alzheimer disease, Parkinson disease, frontotemporal dementia, and healthy control), were spatially normalized using the three methods. The results were then quantitatively compared by using correlation analysis, meta region of interest (meta-ROI) standardized uptake value ratio (SUVR) analysis, and statistical parametric mapping (SPM) analysis.RESULTSThe Pearson correlation coefficient between the images computed by atlas-based method and the gold standard was 0.908 ± 0.005. The relative error of meta-ROI SUVR computed by atlas-based method was 2.12 ± 0.18%. Compared with template-based method, atlas-based method was also more consistent with the gold standard in SPM analysis.CONCLUSIONThe proposed method provides a unified approach to spatially normalize brain PET images of different radiotracers accurately without MR images. A free MATLAB toolbox for this method has been provided.

01 May 2018·Journal of Pharmaceutical and Biomedical AnalysisQ3 · MEDICINE

Developing a cassette microdosing approach to enhance the throughput of PET imaging agent screening

Q3 · MEDICINE

Article

Author: Zhao, Ruiyue ; Liu, Yajing ; Zhang, Yan ; Hong, Haiyan ; Zhang, Aili ; Zhu, Lin ; Sun, Mingyue ; Xiao, Hao ; Zhang, Shuxian ; Qiao, Jinping ; Kung, Hank F ; Liu, Futao

Cassette dosing is also known as N-in-One dosing: several compounds are simultaneously administrated to a single animal and then the samples are rapidly detected by LC-MS/MS. This approach is a successful strategy to enhance the efficiency of drug discovery and reduce animal usage. However, no report on the utility of the cassette approach in radiotracer discovery has appeared in the literature. This study designed a cassette microdose with LC-MS/MS method to enhance the throughput for screening radiopharmaceutical biodistribution in the rat brain directly. Three unradiolabeled compounds (FPBM FPBM2 and AV-133) were chosen as model drugs administrated intravenously to the rats as a cassette as opposed to discrete study. The rat brain biodistribution data, target localization, the differential uptake ratio (%ID/g) and the brain tissue-specific binding ratio were obtained by the LC-MS/MS analysis. These data matched very well with the values obtained by the standard radioactivity measurements. Moreover, no significant differences between discrete dosing and cassette dosing were observed. By circumventing the need for radiolabeled molecules, this method may be high-throughput and safe for the research and development of new PET imaging agents. The combination of cassette microdosing and LC-MS/MS would be a medium throughput screening tool at an early stage in the discovery/development process of PET imaging agents.

06 Jun 2016·ChemMedChemQ3 · MEDICINE

Pancreas‐Specific Delivery of β‐Cell Proliferating Small Molecules

Q3 · MEDICINE

Article

Author: Va, Porino ; Li, Chun ; Hao, Xueshi ; Wu, Tom Y.‐H. ; Laffitte, Bryan ; Shen, Weijun ; Jin, Qihui

AbstractOur research groups recently described a series of small‐molecule inducers of β‐cell proliferation that could be used to increase β‐cell mass. To mitigate the risk of nonspecific proliferation of other cell types, we devised a delivery strategy built on the tissue specificity observed in the experimental β‐cell imaging agent (+)‐dihydrotetrabenazine (DTBZ). The β‐cell proliferator agent aminopyrazine (AP) was covalently linked with (+)‐DTBZ to afford conjugates that retain both the proliferation activity and binding affinity for vesicular monoamine transporter‐2 (VMAT2). In vivo mouse tissue distribution studies of a prototypical AP–DTBZ conjugate showed 15‐fold pancreas exposure over plasma. Tissue‐to‐plasma ratios in liver and kidneys were two‐ and five‐fold, respectively. This work is the first demonstration of enhanced delivery of β‐cell‐proliferating molecules to the pancreas by leveraging the intrinsic tissue specificity of a β‐cell imaging agent.

100 Deals associated with Florbenazine F18

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14945

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Prediabetic State	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Dec 2012
Nerve Degeneration	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Apr 2012
Nerve Degeneration	Phase 3	AU	Avid Radiopharmaceuticals, Inc.	01 Apr 2012
Parkinson Disease	Phase 3	AU	Avid Radiopharmaceuticals, Inc.	01 Apr 2012
Parkinson Disease	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Apr 2012
Diabetes Mellitus, Insulin-Dependent, 2	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Jun 2010
Diabetes Mellitus, Type 2	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Jun 2010
Alzheimer Disease	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Mar 2010
Lewy Body Disease	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Mar 2010
Striatonigral Degeneration	Phase 3	US	Avid Radiopharmaceuticals, Inc.	01 Mar 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01556100 (CTgov)	Phase 2	Parkinson Disease	40	18F-DTBZ AV-133	hkenmfxqjh(gmbomehgab) = vbjfarpqqm jkmoypxbft (jdtvsbtzgu, bogiilxuav - qlexolnvkg) View more	-	15 Dec 2017
NCT01838785 (CTgov)	Phase 2	-	25	18F-DTBZ AV-133	xufirxpbuv(xteersxtqe) = vokhyuwtcy xvuhztnmba (dvykfcpcdq, xumtgltgjy - hcgftsedho) View more	-	25 Sep 2017