Radiosynthesis of [124I]iodometomidate and biological evaluation using small-animal PET

Mol Imaging Biol. 2014 Jun;16(3):317-21. doi: 10.1007/s11307-013-0696-x.

Abstract

Purpose: The application of radiolabelled inhibitors of cytochrome P450 enzymes is a novel approach for molecular imaging of adrenocortical masses to detect adrenal tumours. One potential tracer is radiolabelled iodometomidate (IMTO) with a common option for scintigraphic diagnosis and therapeutic applications. The aim of this study was to radiolabel iodometomidate with the positron-emitting radionuclide iodine-124 ((124)I) for the investigation of the biological behaviour and pharmacokinetics with positron emission tomography (PET).

Procedures: [(124)I]IMTO has been synthesized by oxidative radioiodo-destannylation, purified via semi-preparative HPLC and formulated in acetate-buffered saline, which contained ascorbic acid and ethanol to avoid radiolytic decomposition. Biological evaluation was performed in rats which received 5.5 ± 0.7 MBq [(124)I]IMTO in vivo. The radioactivity distribution (n = 3) has been dynamically imaged from 0-120 min after intravenous (i.v.) injection by small-animal PET. Regions of interest have been defined manually in the reconstructed PET images, and the activity concentration was expressed as percent injected dose per gram tissue (%ID/g).

Results: [(124)I]IMTO was prepared with a radiochemical yield of 83 ± 5 % (n = 3) and a radiochemical purity of >97 %. The final formulation of [(124)I]IMTO was stable for up to 48 h at room temperature. Two hours after i.v. administration in rats, radioactivity concentration in the adrenal glands were 2.1 ± 0.3 %ID/g, which was sufficient to achieve highest-contrast adrenal PET images.

Conclusions: In the present study, the biological characteristics of radioiodinated metomidate were evaluated. [(124)I]IMTO appears as an attractive PET tracer for imaging of adrenals.

MeSH terms

  • Animals
  • Etomidate / analogs & derivatives*
  • Etomidate / chemical synthesis
  • Etomidate / pharmacokinetics
  • Etomidate / pharmacology
  • Female
  • Iodine Radioisotopes / chemistry*
  • Positron-Emission Tomography / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • Iodine Radioisotopes
  • iodophenyl metomidate
  • Etomidate