Synthesis and evaluation of radioiodinated 6-iodo-L-DOPA as a cerebral L-amino acid transport marker

Nucl Med Biol. 1996 Apr;23(3):251-5. doi: 10.1016/0969-8051(95)02054-3.

Abstract

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.

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Biological Transport
  • Brain / drug effects
  • Brain / metabolism
  • Dihydroxyphenylalanine / pharmacology
  • In Vitro Techniques
  • Iodine Radioisotopes* / pharmacokinetics
  • Isotope Labeling / methods
  • Levodopa / analogs & derivatives*
  • Levodopa / chemical synthesis
  • Levodopa / pharmacokinetics
  • Levodopa / pharmacology
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Ouabain / pharmacology
  • Pancreas / metabolism
  • Pancreatin / drug effects
  • Pancreatin / metabolism
  • Rats
  • Tissue Distribution
  • Tomography, Emission-Computed / methods
  • Tyrosine / pharmacology

Substances

  • Amino Acids
  • Iodine Radioisotopes
  • 5-hydroxy-2-iodotyrosine
  • Tyrosine
  • Levodopa
  • Ouabain
  • Dihydroxyphenylalanine
  • Pancreatin