Potential and practical adrenomedullary PET radiopharmaceuticals as an alternative to m-iodobenzylguanidine: m-(omega-[18F]fluoroalkyl)benzylguanidines

Bioconjug Chem. 2004 Jan-Feb;15(1):104-11. doi: 10.1021/bc034115e.

Abstract

To investigate adrenomedullary radiopharmaceuticals for positron emission tomography (PET), we have developed no-carrier-added m-(omega-[18F]fluoroalkyl)benzylguanidines. m-(omega-[18F]Fluoroalkyl)benzylguanidines were prepared in two steps starting from N,N'-bis(tert-butyloxycarbonyl)-N' '-(omega-methanesulfonyloxyalkyl)benzylguanidines in 20-30% radiochemical yields (decay corrected for 100 min) and with high radiochemical purity (>97%) and shown to be stable (>90%) in an in vitro metabolic stability assay. The binding of m-(3-[18F]fluoropropyl)benzylguanidine ((18F]3) to SK-N-SH human neuroblastoma cells was temperature dependent, and binding levels at 4 degrees C were reduced to half of that at 37 degrees C, which was similar to the reduction rate observed for [123I]MIBG. Tissue distribution studies in mice showed the highest uptake in the adrenals (%ID/g = 27.2 +/- 5.0%) with relatively high uptake in the myocardium (%ID/g = 9.3 +/- 0.5%). The results suggest that this radiotracer holds promise as a useful adrenomedullary radiopharmaceutical for PET imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Iodobenzylguanidine / chemistry*
  • 3-Iodobenzylguanidine / pharmacokinetics
  • Animals
  • Antidepressive Agents, Tricyclic / pharmacokinetics
  • Benzylamines / chemical synthesis*
  • Benzylamines / pharmacokinetics
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Chromatography, Thin Layer
  • Desipramine / pharmacokinetics
  • Fluorine Radioisotopes
  • Guanidines / chemical synthesis*
  • Guanidines / pharmacokinetics
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Mice, Inbred ICR
  • Microsomes, Liver / metabolism
  • Neuroblastoma / metabolism
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Antidepressive Agents, Tricyclic
  • Benzylamines
  • Fluorine Radioisotopes
  • Guanidines
  • Indicators and Reagents
  • Radiopharmaceuticals
  • 3-Iodobenzylguanidine
  • Desipramine