Cerebral 6-[F-18]fluoro-L-DOPA uptake in rhesus monkey:pharmacological influence of aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) inhibition

FDOPA/PET scans were performed in one rhesus monkey to study the influence of three catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on FDOPA pharmacokinetics. COMT inhibitors were administered in combination with carbidopa, a peripherally acting inhibitor of the aromatic amino acid decarboxylase (AAAD). FDOPA was administered intravenously and its metabolic fate in plasma was determined using an HPLC system with an on-line gamma-gamma coincidence detector. Cerebral tracer uptake was assessed in the striatum and in a non-dopaminergic brain region (occipital cortex). In the periphery, the pharmacokinetic efficiency of FDOPA was increased due to the combined inhibition of COMT and AAAD activity. All three COMT inhibitors reduced the FDOPA methylation rate constant in plasma, with complete suppression obtained in the case of Ro 40-7592. In the brain, specific F-18 radioactivity (striatal minus brain reference radioactivity) increased as a result of the increase in FDOPA plasma availability following the administration of COMT and AAAD inhibitors. We established a significant linear correlation between striatal radioactivity and FDOPA plasma levels (r = 0.924 +/- 0.048, P <0.0001 for total striatal and r = 0.948 +/- 0.054, P <0.0001 for specific striatal radioactivity). Using plasma FDOPA radioactivity as input, we found that the striatal FDOPA uptake rate constant K-i(FD) was not changed by any of the inhibitors. Thus, the enhancement of striatal radioactivity after application of enzyme inhibitors is a consequence of the increase in plasma FDOPA that becomes available for conversion to fluorodopamine in the striatal dopaminergic nerve terminals. By contrast, using the radioactivity in a non-dopaminergic region (cortex) as input, we found that the striatal FDOPA uptake rate constant K-i(ref) was significantly (P <0.0001) increased following pretreatment with COMT inhibitors. Our analysis demonstrated that K-i(ref) and the 3-OMFD contribution to the cerebral radioactivity were inversely correlated. (C) 1997 Elsevier Science B.V

The quadrupole moment and strong interaction parameters from muonic and pionic X-ray studies of 237Np

The X-ray spectrum of muonic and pionic 237Np has been investigated with muons and pions stopped in a NpO2 target. The nuclear spectroscopic quadrupole moment was determined to be Q=3.886±0.006 b from the splittings of the muonic 5g¿4f hyperfine complexes. The B(E2)¿-values for the first and second excited states were evaluated as 3.17±0.08 and 2.77±0.10 e2b 2, respectively. A comparison between the muonic and pionic 5g¿4f hyperfine complexes yields the strong interaction parameters for the pionic 4f state. For the first time a change of sign as function of Z for the strong interaction quadrupole shift e2(4f) has been observed. The standard optical model predictions agree reasonably well with the measured strong interaction monopole optical shift, e0(4f), and width, ¿0(4f), while they disagree with the experimental value for e2. A stronger s-wave repulsion in the potential could explain this effect