Regional brain uptake and pharmacokinetics of [123I]N-omega-fluoroalkyl-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane esters in baboons

Nucl Med Biol. 1995 Feb;22(2):211-9. doi: 10.1016/0969-8051(94)00096-3.

Abstract

Four N-omega-fluoroalkyl-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane ester (beta-CIT-FE), N-fluoropropyl, methyl ester (beta-CIT-FP), N-fluoroethyl, isopropyl ester (IP-beta-CIT-FE), and N-fluoropropyl, isopropyl ester (IP-beta-CIT-FP)] were labeled with 125I and evaluated in baboons by dynamic SPECT regional brain imaging, measurement of pharmacokinetics in arterial plasma, and whole body imaging. The labeled tracers were prepared by iododestannylation of the corresponding 4-(trimethylstannyl)phenyl compounds in radiochemical yield 63-96% and radiochemical purity > 96%. Regional SPECT brain imaging was carried out over a period of 5 h with a Strichman 810X Brain Imager to assess regional uptake in the striatum and midbrain compared to reference regions in the occipital cortex and cerebellum; arterial blood samples were taken for analysis of metabolites by solvent extraction and HPLC. The methyl esters showed higher total and specific peak uptake in the striatum than the isopropyl esters. Midbrain uptake was uniformly lower than striatal uptake and washed out more rapidly. beta-CIT-FE had more rapid striatal kinetics than beta-CIT-FP, with specific striatal washout rates of 10-14 vs 4-6% peak/h. Biodistribution of [123I] beta-CIT-FE and [123I] beta-CIT-FP measured by whole body conjugate imaging demonstrated major uptake in the brain, liver, and GI tract, with excretion occurring through both the renal and hepatobiliary routes. Absorbed radiation does estimates based on the MIRD schema indicated highest dose rates to the urinary bladder wall and lower large intestine wall (0.7 and 0.6 rad/mCi for [123I] beta-CIT-FE and 0.7 and 0.9 rad/mCi for [123I]beta-CIT-FP, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid
  • Iodine Radioisotopes / metabolism*
  • Iodine Radioisotopes / pharmacokinetics
  • Male
  • Molecular Structure
  • Nortropanes / metabolism*
  • Nortropanes / pharmacokinetics
  • Organ Specificity
  • Papio
  • Structure-Activity Relationship
  • Time Factors
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods

Substances

  • Iodine Radioisotopes
  • Nortropanes