Literature DB >> 36197499

Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP.

Pedro Brugarolas1, Moses Q Wilks2, Jacqueline Noel2, Julia-Ann Kaiser2, Danielle R Vesper2, Karla M Ramos-Torres2, Nicolas J Guehl2, Marina T Macdonald-Soccorso2, Yang Sun2, Peter A Rice2, Daniel L Yokell2, Ruth Lim2, Marc D Normandin2, Georges El Fakhri3.   

Abstract

PURPOSE: [18F]3F4AP is a novel PET radiotracer that targets voltage-gated potassium (K+) channels and has shown promise for imaging demyelinated lesions in animal models of neurological diseases. This study aimed to evaluate the biodistribution, safety, and radiation dosimetry of [18F]3F4AP in healthy human volunteers.
METHODS: Four healthy volunteers (2 females) underwent a 4-h dynamic PET scan from the cranial vertex to mid-thigh using multiple bed positions after administration of 368 ± 17.9 MBq (9.94 ± 0.48 mCi) of [18F]3F4AP. Volumes of interest for relevant organs were manually drawn guided by the CT, and PET images and time-activity curves (TACs) were extracted. Radiation dosimetry was estimated from the integrated TACs using OLINDA software. Safety assessments included measuring vital signs immediately before and after the scan, monitoring for adverse events, and obtaining a comprehensive metabolic panel and electrocardiogram within 30 days before and after the scan.
RESULTS: [18F]3F4AP distributed throughout the body with the highest levels of activity in the kidneys, urinary bladder, stomach, liver, spleen, and brain and with low accumulation in muscle and fat. The tracer cleared quickly from circulation and from most organs. The clearance of the tracer was noticeably faster than previously reported in nonhuman primates (NHPs). The average effective dose (ED) across all subjects was 12.1 ± 2.2 μSv/MBq, which is lower than the estimated ED from the NHP studies (21.6 ± 0.6 μSv/MBq) as well as the ED of other fluorine-18 radiotracers such as [18F]FDG (~ 20 μSv/MBq). No differences in ED between males and females were observed. No substantial changes in safety assessments or adverse events were recorded.
CONCLUSION: The biodistribution and radiation dosimetry of [18F]3F4AP in humans are reported for the first time. The average total ED across four subjects was lower than most 18F-labeled PET tracers. The tracer and study procedures were well tolerated, and no adverse events occurred.
© 2022. The Author(s).

Entities:  

Keywords:  4-Aminopyridine; Biodistribution; Demyelination; First in human; Fluorine-18; IND; Multiple sclerosis; PET; Radiation dosimetry; Voltage-gated potassium channels; [18F]3F4AP

Year:  2022        PMID: 36197499     DOI: 10.1007/s00259-022-05980-w

Source DB:  PubMed          Journal:  Eur J Nucl Med Mol Imaging        ISSN: 1619-7070            Impact factor:   10.057


  10 in total

1.  Column-switching HPLC for the analysis of plasma in PET imaging studies.

Authors:  J Hilton; F Yokoi; R F Dannals; H T Ravert; Z Szabo; D F Wong
Journal:  Nucl Med Biol       Date:  2000-08       Impact factor: 2.408

2.  An efficient new method for the synthesis of 3-[18 F]fluoro-4-aminopyridine via Yamada-Curtius rearrangement.

Authors:  Falguni Basuli; Xiang Zhang; Pedro Brugarolas; Daniel S Reich; Rolf E Swenson
Journal:  J Labelled Comp Radiopharm       Date:  2017-11-30       Impact factor: 1.921

3.  Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis.

Authors:  I Coman; M S Aigrot; D Seilhean; R Reynolds; J A Girault; B Zalc; C Lubetzki
Journal:  Brain       Date:  2006-06-09       Impact factor: 13.501

4.  Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial.

Authors:  Andrew D Goodman; Theodore R Brown; Lauren B Krupp; Randall T Schapiro; Steven R Schwid; Ron Cohen; Lawrence N Marinucci; Andrew R Blight
Journal:  Lancet       Date:  2009-02-28       Impact factor: 79.321

5.  4-Aminopyridine improves clinical signs in multiple sclerosis.

Authors:  D Stefoski; F A Davis; M Faut; C L Schauf
Journal:  Ann Neurol       Date:  1987-01       Impact factor: 10.422

6.  Radiation dosimetry of 18F-FDG PET/CT: incorporating exam-specific parameters in dose estimates.

Authors:  Brian Quinn; Zak Dauer; Neeta Pandit-Taskar; Heiko Schoder; Lawrence T Dauer
Journal:  BMC Med Imaging       Date:  2016-06-18       Impact factor: 1.930

7.  Identification of metabolites of dalfampridine (4-aminopyridine) in human subjects and reaction phenotyping of relevant cytochrome P450 pathways.

Authors:  Anthony Caggiano; Andrew Blight
Journal:  J Drug Assess       Date:  2013-08-14

8.  Development of a PET radioligand for potassium channels to image CNS demyelination.

Authors:  Pedro Brugarolas; Jorge E Sánchez-Rodríguez; Hsiu-Ming Tsai; Falguni Basuli; Shih-Hsun Cheng; Xiang Zhang; Andrew V Caprariello; Jerome J Lacroix; Richard Freifelder; Dhanabalan Murali; Onofre DeJesus; Robert H Miller; Rolf E Swenson; Chin-Tu Chen; Peter Herscovitch; Daniel S Reich; Francisco Bezanilla; Brian Popko
Journal:  Sci Rep       Date:  2018-01-12       Impact factor: 4.379

9.  Detecting Demyelination by PET: The Lesion as Imaging Target.

Authors:  Pedro Brugarolas; Daniel S Reich; Brian Popko
Journal:  Mol Imaging       Date:  2018 Jan-Dec       Impact factor: 4.488

10.  Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques.

Authors:  Nicolas J Guehl; Karla M Ramos-Torres; Clas Linnman; Sung-Hyun Moon; Maeva Dhaynaut; Moses Q Wilks; Paul K Han; Chao Ma; Ramesh Neelamegam; Yu-Peng Zhou; Brian Popko; John A Correia; Daniel S Reich; Georges El Fakhri; Peter Herscovitch; Marc D Normandin; Pedro Brugarolas
Journal:  J Cereb Blood Flow Metab       Date:  2020-10-22       Impact factor: 6.200

  10 in total

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