Synthesis, in vivo rhesus monkey biodistribution and in vitro evaluation of a 11C-labelled potent aromatase inhibitor: [N-methyl-11C]vorozole

Nucl Med Biol. 1998 Jul;25(5):497-501. doi: 10.1016/s0969-8051(98)00009-2.

Abstract

[N-methyl-11C]Vorozole, a high-affinity aromatase-binding radiotracer, was synthesized through N-methylation of the corresponding nor-vorozole derivative using [11C]methyl iodide. [N-methyl-11C]Vorozole was obtained in 53-56% radiochemical yield based on [11C]methyl iodide within 40 min of the end of radionuclide production. The final formulation was >98% radiochemically pure and had a specific radioactivity of 10-143 GBq/micromol. In vitro, [N-methyl-11C]vorozole displayed high and specific binding to aromatase-rich human placenta. [N-methyl-11C]Vorozole binding to other tissues was lower and less specific. The dissociation constant measured was in the low nM range (Kd 1.7 nM), consistent with published Ki values for vorozole. Biodistribution studies in rhesus monkeys showed high liver uptake, which reached a constant level of 20% of the injected dose after 10 min, and an otherwise relatively even distribution of radioactivity. Pretreatment with vorozole only caused minor alterations of the biodistribution of the tracer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatase Inhibitors*
  • Autoradiography
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • In Vitro Techniques
  • Macaca mulatta
  • Placenta / metabolism
  • Swine
  • Tissue Distribution

Substances

  • Aromatase Inhibitors
  • Enzyme Inhibitors