Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine

Una D. McCann; Zsolt Szabo; Melin Vranesic; Esen Seckin; Gary Wand; Anna DuVal; Robert F. Dannals; George A. Ricaurte

doi:10.1007/s11307-007-0082-7

Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine

Una D. McCann, Zsolt Szabo, Melin Vranesic, Esen Seckin, Gary Wand, Anna DuVal, Robert F. Dannals, George A. Ricaurte

School of Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Purpose: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997. Both drugs are known to have the potential to damage brain serotonin (5-HT) axons and axon terminals in animals, including nonhuman primates. This study used quantitative positron emission tomography (PET) with [¹¹C] McN5652, a serotonin transporter (SERT) ligand to determine whether humans previously exposed to fenfluramines showed reductions in SERT binding parameters. Procedures: Subjects previously treated with fenfluramines for weight loss (N=15) and age-matched controls (N=17) underwent PET studies with [¹¹C] McN5652. Global and regional distribution volumes (DVs) of [¹¹C] McN5652 were compared in the two subject groups using parametric statistical analyses. Results: Compared to controls, subjects previously exposed to fenfluramines had significant reductions in [¹¹C]McN5652 binding in 14 of 15 regions of interest, more than four years after drug discontinuation. Conclusions: These results are the first to provide direct evidence for fenfluramine-induced 5-HT neurotoxicity in humans.

Original language	English (US)
Pages (from-to)	151-157
Number of pages	7
Journal	Molecular Imaging and Biology
Volume	9
Issue number	3
DOIs	https://doi.org/10.1007/s11307-007-0082-7
State	Published - May 2007

Keywords

Amphetamines
Neurotoxicity
Serotonin

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1007/s11307-007-0082-7

Cite this

McCann, U. D., Szabo, Z., Vranesic, M., Seckin, E., Wand, G., DuVal, A., Dannals, R. F., & Ricaurte, G. A. (2007). Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine. Molecular Imaging and Biology, 9(3), 151-157. https://doi.org/10.1007/s11307-007-0082-7

McCann, UD , Szabo, Z, Vranesic, M, Seckin, E, Wand, G, DuVal, A, Dannals, RF & Ricaurte, GA 2007, 'Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine', Molecular Imaging and Biology, vol. 9, no. 3, pp. 151-157. https://doi.org/10.1007/s11307-007-0082-7

@article{a3f6f084227c49edb7c7b0dd78e1313e,

title = "Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine",

abstract = "Purpose: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997. Both drugs are known to have the potential to damage brain serotonin (5-HT) axons and axon terminals in animals, including nonhuman primates. This study used quantitative positron emission tomography (PET) with [11C] McN5652, a serotonin transporter (SERT) ligand to determine whether humans previously exposed to fenfluramines showed reductions in SERT binding parameters. Procedures: Subjects previously treated with fenfluramines for weight loss (N=15) and age-matched controls (N=17) underwent PET studies with [11C] McN5652. Global and regional distribution volumes (DVs) of [11C] McN5652 were compared in the two subject groups using parametric statistical analyses. Results: Compared to controls, subjects previously exposed to fenfluramines had significant reductions in [11C]McN5652 binding in 14 of 15 regions of interest, more than four years after drug discontinuation. Conclusions: These results are the first to provide direct evidence for fenfluramine-induced 5-HT neurotoxicity in humans.",

keywords = "Amphetamines, Neurotoxicity, Serotonin",

author = "McCann, {Una D.} and Zsolt Szabo and Melin Vranesic and Esen Seckin and Gary Wand and Anna DuVal and Dannals, {Robert F.} and Ricaurte, {George A.}",

note = "Funding Information: This research was supported by several grants from the National Institute of Health (NIH), which are cited in the Acknowledgments section. The NIH was not involved in the study design, subject recruitment, execution of the study, data analysis or interpretation, writing of the manuscript, decision to submit the manuscript for publication. Funding Information: Acknowledgments. This manuscript was supported by PHS Grants DA00206 (Ricaurte); AA11653 (Szabo), NSF Grant No. 843 (Szabo), and NCRR grant M01RR002719 (Klag). We thank Paul Nuzzo for his assistance with statistical analyses, and Audra de Ridder for her assistance with recruiting subjects. We appreciate the important contributions of Jozsef Varga, Ph.D. whose work was pivotal for the development of the image analysis package PMT that was used in this project.",

year = "2007",

month = may,

doi = "10.1007/s11307-007-0082-7",

language = "English (US)",

volume = "9",

pages = "151--157",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

number = "3",

}

TY - JOUR

T1 - Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine

AU - McCann, Una D.

AU - Szabo, Zsolt

AU - Vranesic, Melin

AU - Seckin, Esen

AU - Wand, Gary

AU - DuVal, Anna

AU - Dannals, Robert F.

AU - Ricaurte, George A.

N1 - Funding Information: This research was supported by several grants from the National Institute of Health (NIH), which are cited in the Acknowledgments section. The NIH was not involved in the study design, subject recruitment, execution of the study, data analysis or interpretation, writing of the manuscript, decision to submit the manuscript for publication. Funding Information: Acknowledgments. This manuscript was supported by PHS Grants DA00206 (Ricaurte); AA11653 (Szabo), NSF Grant No. 843 (Szabo), and NCRR grant M01RR002719 (Klag). We thank Paul Nuzzo for his assistance with statistical analyses, and Audra de Ridder for her assistance with recruiting subjects. We appreciate the important contributions of Jozsef Varga, Ph.D. whose work was pivotal for the development of the image analysis package PMT that was used in this project.

PY - 2007/5

Y1 - 2007/5

N2 - Purpose: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997. Both drugs are known to have the potential to damage brain serotonin (5-HT) axons and axon terminals in animals, including nonhuman primates. This study used quantitative positron emission tomography (PET) with [11C] McN5652, a serotonin transporter (SERT) ligand to determine whether humans previously exposed to fenfluramines showed reductions in SERT binding parameters. Procedures: Subjects previously treated with fenfluramines for weight loss (N=15) and age-matched controls (N=17) underwent PET studies with [11C] McN5652. Global and regional distribution volumes (DVs) of [11C] McN5652 were compared in the two subject groups using parametric statistical analyses. Results: Compared to controls, subjects previously exposed to fenfluramines had significant reductions in [11C]McN5652 binding in 14 of 15 regions of interest, more than four years after drug discontinuation. Conclusions: These results are the first to provide direct evidence for fenfluramine-induced 5-HT neurotoxicity in humans.

AB - Purpose: The appetite suppressants fenfluramine and dexfenfluramine were widely prescribed before being withdrawn from the market in 1997. Both drugs are known to have the potential to damage brain serotonin (5-HT) axons and axon terminals in animals, including nonhuman primates. This study used quantitative positron emission tomography (PET) with [11C] McN5652, a serotonin transporter (SERT) ligand to determine whether humans previously exposed to fenfluramines showed reductions in SERT binding parameters. Procedures: Subjects previously treated with fenfluramines for weight loss (N=15) and age-matched controls (N=17) underwent PET studies with [11C] McN5652. Global and regional distribution volumes (DVs) of [11C] McN5652 were compared in the two subject groups using parametric statistical analyses. Results: Compared to controls, subjects previously exposed to fenfluramines had significant reductions in [11C]McN5652 binding in 14 of 15 regions of interest, more than four years after drug discontinuation. Conclusions: These results are the first to provide direct evidence for fenfluramine-induced 5-HT neurotoxicity in humans.

KW - Amphetamines

KW - Neurotoxicity

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=34248224268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248224268&partnerID=8YFLogxK

U2 - 10.1007/s11307-007-0082-7

DO - 10.1007/s11307-007-0082-7

M3 - Article

C2 - 17473958

AN - SCOPUS:34248224268

SN - 1536-1632

VL - 9

SP - 151

EP - 157

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 3

ER -

Quantitative positron emission tomography studies of the serotonin transporter in humans previously treated with the appetite suppressants fenfluramine or dexfenfluramine

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this