In vivo and in vitro characterization of R(+)-FIDA2, a novel dopamine D2/D3 receptor imaging agent
- Univ. of Pennsylvania, Philadelphia, PA (United States); and others
FIDA2, (R)-(+)-2,3-dimethoxy-5-iodo-N-[1-(4`-fluorobenzyl)-2-pyrrolidinyl)-methyl]benzamide, is a new dopamine D2/D3 receptor imaging agent that can be labeled with either I-123 or F-18 for SPECT or PET imaging. In vitro binding studies of I-125 FIDA2 using dopamine D2 or D3 receptors expressed in Sf9 cells showed Kd values of 0.04 and 0.05 nM, respectively. In rat striatal homogenates, which contain a high density of dopamine D2 receptors, the ligand displayed a Kd of 0.04-0.06 nM. A series of in vivo SPECT images (transaxial sections, 2 mm) showed the radioactivity was localized in the area of the basal ganglia and reached peak concentrations in 11.2 {plus_minus} 5.9 min. The activity cleared at a rate of 33.5 {plus_minus} 9.4 %/hr. The target to nontarget ratios (basal ganglia to cerebellum) at time of peak, 1 hr, 2 hr and 3 hr p.i., were 1.1 {plus_minus} 0.4 (n=21), 3.5 {plus_minus} 1.0 (n=20), 6.3 {plus_minus} 2.9 (n=9, and 8.14 {plus_minus} 4.7 (n=9), respectively. At 90 min an injection of haloperidol or raclopride, dopamine D2/D3 receptor antagonists, displaced target activity but an injection of SCH23390, a dopamine D1 receptor antagonist, had little effect on activity in the basal ganglia. In addition, an injection of R-(+)-7-OH-PIPAT, a new ligand that is selective for the dopamine D3 receptor and the high affinity state of the dopamine D2 receptor, showed partial displacement ({approximately}15%) of I-123 FIDA2 binding in the basal ganglia. These studies indicate that FIDA2 may be a useful ligand for in vivo imaging of dopamine D2/D3 receptors.
- OSTI ID:
- 197995
- Report Number(s):
- CONF-940605--; CNN: Grant NS-24538
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 35; ISSN JNMEAQ; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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