A novel electrophilic synthesis and evaluation of medium specific radioactivity (1R,2S)-4-[18F]fluorometaraminol, a tracer for the assessment of cardiac sympathetic nerve integrity with PET.
(1R,2S)-4-[18F]fluorometaraminol (4-[18F]FMR), a tracer for cardiac sympathetic innervation, was synthesized by electrophilic aromatic substitution. A trimethylstannyl precursor, protected with tert-butoxycarbonyl protecting groups, was radiofluorinated with high specific radioactivity [18F]F2. Specific radioactivity of 4-[18F]FMR, in average 11.8 +/-3.3 GBq/micromol, was improved 40-800-fold in comparison to the previous electrophilic fluorinations. The biodistribution of 4-[18F]FMR in rat was in accordance with the known distribution of sympathetic innervation. 4-[18F]FMR showed no metabolic degradation in left ventricle of rat heart, where the uptake was high, rapid and specific.
Eskola
Olli
O
Turku PET Centre, Radiopharmaceutical Chemistry Laboratory and Accelerator Laboratory, Porthaninkatu 3, FIN 20500, Turku, Finland. olesko@utu.fi
Grönroos
Tove
T
Bergman
Jörgen
J
Haaparanta
Merja
M
Marjamäki
Päivi
P
Lehikoinen
Pertti
P
Forsback
Sarita
S
Langer
Oliver
O
Hinnen
Françoise
F
Dollé
Frédéric
F
Halldin
Christer
C
Solin
Olof
O
D000818:Animals; D001711:Biotransformation; D001822:Body Burden; D004563:Electrochemistry / Q000379:methods; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000294:innervation / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008680:Metaraminol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D009638:Norepinephrine / Q000378:metabolism*; D009928:Organ Specificity; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods
C413488:4-fluorometaraminol; D019275:Radiopharmaceuticals; D008680:Metaraminol; D009638:Norepinephrine