ABSTRACT
A novel PET probe, 6-[(11)C]methyl-m-tyrosine ([(11)C]6MemTyr), was developed for quantitative imaging of presynaptic dopamine (DA) synthesis in the living brain using positron emission tomography (PET). This probe was evaluated by comparison with conventional 6-[(18)F]fluoro-l-dopa ([(18)F]FDOPA). [(11)C]6MemTyr was labeled using rapid Pd(0)-mediated C-[(11)C]methylation with [(11)C]methyl iodide. The synthesis time was only 35min, and its radiochemical yield was 76%, with radiochemical purity of >99%. PET measurements indicated that [(11)C]6MemTyr could image presynaptic DA synthesis in the striatum of living monkey brain, providing much higher contrast between the striatum and the cerebellum than that with [(18)F]FDOPA.
Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Carbon Radioisotopes/analysis , Dopamine/analysis , Methyltyrosines/analysis , Positron-Emission Tomography/methods , Animals , Carbon Radioisotopes/metabolism , Corpus Striatum/diagnostic imaging , Corpus Striatum/metabolism , Dopamine/metabolism , Fluorine Radioisotopes/analysis , Fluorine Radioisotopes/metabolism , Levodopa/analysis , Macaca fascicularis , Male , Methyltyrosines/chemical synthesis , Methyltyrosines/metabolism , Radiopharmaceuticals/analysis , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/metabolismABSTRACT
A simple and sensitive polarographic method is described for the determination of metyrosine through treatment with nitrous acid. The different experimental parameters affecting the derivatization process, as well as the polarographic analysis were studied. The derivatization product was found to be reducible at the dropping mercury electrode over the whole pH range in Britton Robinson buffers. At pH 5, a well-defined diffusion-controlled cathodic wave was produced. The limiting current versus the concentration plot was linear over the range 8-80 mumol/l in the direct current mode with a detection limit of 0.2 mumol/l. The method was then applied to the determination of metyrosine capsules, and the results obtained were in good agreement with those given by the USP method.
Subject(s)
Methyltyrosines/analysis , Nitrous Acid , Polarography , Tyrosine 3-Monooxygenase/antagonists & inhibitors , Methyltyrosines/chemistry , Models, Chemical , alpha-MethyltyrosineABSTRACT
Transsphenoidal hypophysectomy was performed in 13 patients with advanced malignant melanoma. Although three minor responses were observed, there were no complete or partial responses. All three patients with bone pain had a decrease in discomfort lasting 1-2 months. All five patients with minor responses or stable disease had postoperative decreases in the excretion of the dihydroxyphenylalanine (DOPA) metabolite 3-O-methyldopamine; all but one patient with clinical progression had postoperative increases in excretion. Average survival of those whose postoperative excretion fell (143 +/- days; range, 60-217+) was significantly longer (P less than 0.004) than that of those whose postsurgical values rose (30 days; range, 15-58).
