Synthesis and biodistribution of a new radiotracer for in vivo labeling of serotonin uptake sites by PET, cis-N,N-[11C]dimethyl-3-(2',4'-dichlorophenyl)-indanamine (cis-[11C]DDPI).
A new PET radiotracer for in vivo labeling of serotonin (5-HT) uptake sites, cis-N,N-[11C]dimethyl-3-(2',4'-dichlorophenyl)-indanamine, cis-[11C]DDPI, was synthesized and its biological behavior was studied. The radiosynthesis of cis-[11C]DDPI was performed by N-methylation of cis-N-methyl-3-(2',4'-dichlorophenyl)-indanamine with [11C]iodomethane. The average radiochemical yield was approx. 8%, with an average specific activity of 600 mCi/mumol. Following intravenous administration, cis-[11C]DDPI accumulated in mouse brain regions rich in 5-HT uptake sites, such as olfactory tubercles, hypothalamus and frontal cortex. Following pre-injection of 1 mg/kg of paroxetine, a high affinity 5-HT uptake blocker, the binding of cis-[11C]DDPI in the olfactory tubercles, hypothalamus and frontal cortex was decreased by 23, 25 and 16%; this corresponds to 73, 82 and 59% of the specific binding in these regions. These results suggest that the accumulation of cis-[11C]DDPI in the tissues rich in 5-HT sites is a result of specific binding of cis-[11C]DDPI to 5-HT uptake sites. Due to the relatively high non-specific uptake and slow clearance of this compound from non-specific binding sites, the ratio between specific and non-specific binding increased slowly with time, reaching 1.5:1 at 60 min after injection.
Suehiro
M
M
Division of Nuclear Medicine and Radiation Health Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
Scheffel
U
U
Dannals
R F
RF
Wilson
A A
AA
Ravert
H T
HT
Wagner
H N
HN
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D007189:Indans / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D007189:Indans; D011985:Receptors, Serotonin; D012701:Serotonin; C076870:N,N-dimethyl-3-(2',4'-dichlorophenyl)indanamine