Article Figures & Data
Figures
- FIGURE 1.
Synthesis of labeling precursor for 11C-CIMBI-5 (3): (a) 2-(tert-butyldimethylsilyloxy)benzaldehyde, NaBH4, MeOH; (b) Boc2O, THF; and (c) TBAF, NH4Cl, THF. OTBDMS = t-butyldimethylsiloxy; THF = tetrahydrofuran.
- FIGURE 2.
Radiochemical synthesis of 11C-CIMBI-5. OTf = triflate; TFA = trifluoroacetic acid.
- FIGURE 3.
Time-dependent ex vivo distribution of 11C-CIMBI-5 and displacement by ketanserin. (A) SBRs in frontal cortex in rats are shown relative to time after injection. (B) After ketanserin pretreatment (1 mg/kg intravenously), SBR in frontal cortex at 30 min after 11C-CIMBI-5 injection is significantly decreased. ***P < 0.0001 in Student t test of ketanserin vs. saline. ROI = region of interest.
- FIGURE 4.
Representative coronal (top), sagittal (middle), and horizontal (bottom) PET images summed from 0 to 90 min of scanning showing distribution of 11C-CIMBI-5 in pig brain. Left column shows PET images after 3 × 3 × 3 mm gaussian filtering. Right column shows same PET images aligned and overlaid on a standardized MRI-based atlas of the pig brain after coregistration. SUV = standardized uptake value.
- FIGURE 5.
Time–activity curves of 5-HT2A agonist and antagonist PET tracers in pig brain. (A) 11C-CIMBI-5 time–activity curves in Danish Landrace pig brain at baseline (black solid line) or after intravenous ketanserin (3 mg/kg bolus, 1 mg/kg/h infusion) blockade (gray dotted line). (B) 18F-altanserin time–activity curves in minipigs. Mean standardized uptake values normalized to injected dose per body weight are shown. SUV = standardized uptake value.
- FIGURE 6.
HPLC analysis of radioactive metabolites in pig plasma after intravenous injection of 11C-CIMBI-5. ▪ = parent compound 11C-CIMBI-5; ▾ = lipophilic metabolite; •= polar metabolites.
- FIGURE 7.
HPLC analysis of brain extracts and plasma at 25 min after injection of 11C-CIMBI-5: frontal cortex (A), cerebellum (B), and plasma (C). Peaks: 1 = polar metabolites, 2 = lipophilic metabolites, and 3 = parent compound.
Tables
- TABLE 1
PDSP Screening Result: Inhibition Constants (Ki) for CIMBI-5 Versus Serotonin and Other Receptors
Receptor Ki (nM) 5-HT2A 2.2 ± 0.1 5-HT2B 2.3 ± 0.2 5-HT2C 7.0 ± 1.0 5-HT6 58 ± 17 5-HT1A 85 ± 16 D3 117 ± 14 α2C 348 ± 17 D4 647 ± 37 Serotonin transporter 1,009 ± 84 α2A 1,106 ± 206 M5 1,381 ± 231 D2 1,600 ± 333 5-HT7 1,670 ± 125 5-HT5A 2,200 ± 385 D1 3,718 ± 365 5-HT1B 3,742 ± 553 Norepinephrine transporter 4,574 ± 270 Dopamine transporter 5,031 ± 343 D5 7,872 ± 933
Supplemental Data
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