Synthesis and evaluation of radioiodinated 6-iodo-L-DOPA as a cerebral L-amino acid transport marker.
Regioselective radioiodination of N-trifluoroacetyl 3,4-dimethoxy-6-trifluoroacetoxymercurio-L-phenylalanine ethyl ester 1 under no-carrier-added condition gave 6-[125I]iodo protected L-DOPA with a labeling efficiency of more than 85%, and no-carrier-added 6-[125I]I-L-DOPA was obtained with a radio-chemical purity of over 95% after hydrolysis and chromatography. A nonradioactive standard of 6-iodo protected L-DOPA was synthesized by the iododemercuration of 6-mercuric trifluoroacetate protected L-DOPA 1 using I2 in chloroform. 6-[125I]I-L-DOPA showed high brain accumulation and rapid blood clearance in mice. The rat brain slice studies indicated high affinity of 6-[125I]I-L-DOPA for carrier-mediated and stereoselective active transport systems. The tissue homogenate analysis revealed that most of the accumulated radioactivity was intact 6-[125I]I-L-DOPA. Thus, 6-[123I]I-L-DOPA appears to be a suitable single photon emission computed tomography (SPECT) tracer for the selective measurement of cerebral L-amino acid transport, having no affinity for dopamine metabolism.
Kawai
K
K
Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Ohta
H
H
Kubodera
A
A
Channing
M A
MA
Eckelman
W C
WC
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D007980:Levodopa / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010042:Ouabain / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism; D010194:Pancreatin / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods; D014443:Tyrosine / Q000494:pharmacology
D000596:Amino Acids; D007457:Iodine Radioisotopes; C102270:5-hydroxy-2-iodotyrosine; D014443:Tyrosine; D007980:Levodopa; D010042:Ouabain; D004295:Dihydroxyphenylalanine; D010194:Pancreatin