Article Figures & Data
Figures
- FIGURE 1.
Chemical structures of radioligands and candidate metabolites of TASP699. * = methoxy moiety to be radiolabeled with 11C.
- FIGURE 2.
PET images of the head of an isoflurane-anesthetized rhesus monkey after intravenous injection of radioligands. (A) Representative coronal PET images after injection of 11C-TASP699 (top) and 11C-TASP0434299 (bottom). Images were averaged at 30–90 min after radioligand administration and were coregistered with cranial MR image of same monkey. Arrows indicate pituitary. (B) Representative time–radioactivity curve in pituitary (filled circles), temporal muscle (crosses), and whole brain (filled rhombi) after injection of 11C-TASP699, and in pituitary after injection of 11C-TASP0434299 (open triangles). (C and D) Representative reversed-phase high-performance liquid chromatograms of protein-precipitated plasma samples at 30 (C) and 60 (D) min after injection of 11C-TASP699. Injection volumes of supernatant into HPLC were 0.43 mL (C) and 0.95 mL (D).
- FIGURE 3.
(A and B) Time–activity curves in pituitary and plasma of monkeys 1 (A) and 2 (B) after intravenous injection of 11C-TASP699 with or without pretreatment with TASP0390325. (C and D) Time course of venous plasma radioactivity originating from parent in monkeys 1 (C) and 2 (D).
- FIGURE 4.
Autoradiographic labeling of pituitary slices prepared from rhesus monkey with 11C-TASP699. (A) Representative images of pituitary samples autoradiographically labeled with 11C-TASP699 without blockade (control) or with decreasing concentrations of TASP0390325 and of TASP0233278. Scale bar = 10 mm. (B) Specific binding of 11C-TASP699 to slices inhibited by TASP0390325 (n = 3 in each condition) and TASP0233278 (n = 1 in each condition) in concentration-dependent fashion. Error bars for TASP0390325 data represent SEM.
Tables
3H-AVP binding Compound/peptide Human V1B receptor Human V1A receptor Human V2 receptor 3H-oxytocin binding, human oxytocin receptor [Ca2+]i assay, human V1B receptor TASP699 0.165 >10,000 >10,000 >10,000 0.381 Metabolite candidate 1 >1,000 — — — — Metabolite candidate 2 1.87 — — — — TASP0434299 0.526 >10,000 >10,000 >10,000 0.639 AVP 0.776 0.440 1.24 — — Oxytocin — — — 0.731 — — = not determined.
IC50 values (nM) are expressed as geometric means (n = 3–6).
Supplemental Data
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