Synthesis and evaluation of novel tropane derivatives as potential PET imaging agents for the dopamine transporter.
A novel series of tropane derivatives containing a fluorinated tertiary amino or amide at the 2β position was synthesized, labeled with the positron-emitter fluorine-18 (t(1/2)=109.8 min), and tested as potential in vivo dopamine transporter (DAT) imaging agents. The corresponding chlorinated analogs were prepared and employed as precursors for radiolabeling leading to the fluorine-18-labeled derivatives via a one-step nucleophilic aliphatic substitution reaction. In vitro binding results showed that the 2β-amino compounds 6b, 6d and 7b displayed moderately high affinities to DAT (K(i)<10nM). Biodistribution studies of [(18)F]6b and [(18)F]6d showed that the brain uptakes in rats were low. This is likely due to their low lipophilicities. Further structural modifications of these tropane derivatives will be needed to improve their in vivo properties as DAT imaging agents.
Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875, PR China.
Hongwen
H
Qiao
Lin
L
Zhu
Brian P
BP
Lieberman
Zhihao
Z
Zha
Karl
K
Plössl
Hank F
HF
Kung
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014326:Tropanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D003287:Contrast Media; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D014326:Tropanes