Novel electrophilic synthesis of 6-[18F]fluorodopamine and comprehensive biological evaluation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-05

AUTHORS

Olli Eskola, Tove J. Grönroos, Alexandru Naum, Päivi Marjamäki, Sarita Forsback, Jörgen Bergman, Sami Länkimäki, Jan Kiss, Timo Savunen, Juhani Knuuti, Merja Haaparanta, Olof Solin

ABSTRACT

PURPOSE: 6-[(18)F]Fluorodopamine (4-(2-aminoethyl)-5-[(18)F]fluorobenzene-1,2-diol, 6-[(18)F]FDA) is a tracer for imaging sympathetically innervated tissues. Previous electrophilic labelling methods produced 6-[(18)F]FDA with low specific radioactivity (SA) which has limited its wider use. Our aim was to employ electrophilic labelling and increase the SA to around 15 GBq/μmol. We also sought to determine an extensive biodistribution pattern for 6-[(18)F]FDA in rats in order to thoroughly identify tissues with dense sympathetic innervation that were specifically labelled with 6-[(18)F]FDA. In addition, to investigate the safety profile of 6-[(18)F]FDA in larger animals, we performed in vivo studies in pigs. METHODS: 6-[(18)F]FDA was synthesised using high SA electrophilic [(18)F]F(2) as the labelling reagent. Biodistribution and metabolism of 6-[(18)F]FDA was determined ex vivo in rats, and in vivo studies were done in pigs. RESULTS: 6-[(18)F]FDA was synthesised with 2.6 ± 1.1% radiochemical yield. The total amount of purified 6-[(18)F]FDA was 663 ± 291 MBq at the end of synthesis (EOS). SA, decay corrected to EOS, was 13.2 ± 2.7 GBq/μmol. Radiochemical purity exceeded 99.0%. Specific uptake of 6-[(18)F]FDA was demonstrated in heart, lung, pancreas, adrenal gland, lower large intestine (LLI), eye, thyroid gland, spleen and stomach tissue. 6-[(18)F]FDA in rat plasma declined rapidly, with a half-life of 2 min, indicating fast metabolism. In vivo PET studies in pigs confirmed the tracer could be used safely without pharmacological effects. CONCLUSION: 6-[(18)F]FDA was synthesised with good radiopharmaceutical quality and yields high enough for several human PET studies. The SA of 6-[(18)F]FDA was improved by 50- to 500-fold compared to previous electrophilic methods. Uptake of 6-[(18)F]FDA was specific in various peripheral organs, indicating that 6-[(18)F]FDA PET can be used to investigate sympathoneural functions beyond cardiac studies when higher specific uptake is achieved. More... »

PAGES

800-810

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00259-011-2032-5

DOI

http://dx.doi.org/10.1007/s00259-011-2032-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016372264

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22231017


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00259-011-2032-5'

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00259-011-2032-5'


 

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286 https://www.grid.ac/institutes/grid.412008.f schema:alternateName Haukeland University Hospital
287 schema:name Nuclear Medicine/PET Center, Department of Radiology, Haukeland University Hospital, Bergen, Norway
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289 https://www.grid.ac/institutes/grid.470895.7 schema:alternateName Turku PET Centre
290 schema:name Turku PET Centre, Accelerator Laboratory, Åbo Akademi University, Turku, Finland
291 Turku PET Centre, University of Turku, Medicity/PET Preclinical Imaging, Turku, Finland
292 Turku PET Centre, University of Turku, Radiopharmaceutical Chemistry Laboratory, Kiinamyllynkatu 4-8, 20520, Turku, Finland
293 Turku PET Centre, University of Turku, Turku, Finland
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295 https://www.grid.ac/institutes/grid.7708.8 schema:alternateName University Medical Center Freiburg
296 schema:name Department of Cardiovascular Surgery, University Medical Center Freiburg, Freiburg, Germany
297 rdf:type schema:Organization
 




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