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 600mCi/μmol. 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.