[18F]desmethoxyfallypride as a novel PET radiotracer for quantitative in vivo dopamine D2/D3 receptor imaging in rat models of neurodegenerative diseases

Nucl Med Biol. 2012 Oct;39(7):1077-80. doi: 10.1016/j.nucmedbio.2012.04.003. Epub 2012 May 15.

Abstract

Introduction: [(18)F]desmethoxyfallypride ([(18)F]DMFP) is a promising tracer for longitudinal assessment of striatal dopamine D2/D3-receptor (D2R) availability by positron emission tomography (PET) in small animal models. We explored the feasibility of [(18)F]DMFP-PET to image D2R availability in rat models of Huntington's (HD) and Parkinson's disease (PD).

Methods: Animals received either unilateral intrastriatal quinolinic acid lesions or medial forebrain bundle injections of 6-OHDA to produce the loss of striatal projection neurones or deplete the striatal dopamine, corresponding to established animal models for HD and PD, respectively. Three weeks after lesioning, PET scans were acquired on a microPET Focus 120 system following the tail vein injection of [(18)F]DMFP.

Results: [(18)F]DMFP-PET clearly visualized lesion induced decreases and increases of D2R availability. In vivo estimates of D2R binding and changes thereof gained by pharmacokinetic analyses correlated significantly with D2R density and its change provided by in vitro [(3)H]raclopride-autoradiography.

Conclusions: In conclusion, [(18)F]DMFP-PET is a suitable method for in vivo D2R-assessment in preclinical research, e.g for monitoring cell-based therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Huntington Disease / diagnostic imaging
  • Huntington Disease / metabolism*
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / metabolism*
  • Positron-Emission Tomography / methods*
  • Raclopride / metabolism
  • Radioactive Tracers
  • Rats
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Salicylamides*

Substances

  • Radioactive Tracers
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Salicylamides
  • desmethoxyfallypride
  • Raclopride