Copper(II) bis(thiosemicarbazone) complexes as potential tracers for evaluation of cerebral and myocardial blood flow with PET

J Nucl Med. 1988 Sep;29(9):1549-57.

Abstract

Wider application of positron emission tomography would be facilitated by the availability of positron-emitting radiopharmaceuticals labeled with nuclides, like 62Cu, that are available from parent/daughter generator systems. Using a longer-lived copper isotope (67Cu) we have examined three derivatives of copper(II) pyruvaldehyde bis(thiosemicarbazone) as potential tracers for evaluation of cerebral and myocardial blood flow: Cu(PTS), Cu(PTSM), and Cu(PTSM2) (where PTS = pyruvaldehyde bis(thiosemicarbazone), PTSM = pyruvaldehyde bis(N4-methylthiosemicarbazone), and PTSM2 = pyruvaldehyde bis(N4-dimethylthiosemicarbazone). All three lipophilic radiocopper complexes were obtained in high yield via a procedure that could be adapted to a "kit" formulation. In animal model systems Cu(PTSM) and Cu(PTSM2) show excellent uptake in the brain and heart following i.v. injection. These tracers differ in that Cu(PTSM) exhibits microsphere-like retention in the brain and heart, whereas Cu(PTSM2) substantially clears from these organs. The relative cerebral pharmacokinetics of [67Cu]Cu(PTSM) and [67Cu]Cu(PTSM2) are consistent with their known reactivity towards intracellular sulfhydryl groups.

Publication types

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

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Cerebrovascular Circulation*
  • Copper Radioisotopes*
  • Coronary Circulation*
  • Gerbillinae
  • Heart / diagnostic imaging*
  • Macaca fascicularis
  • Male
  • Organometallic Compounds*
  • Radionuclide Generators
  • Rats
  • Rats, Inbred Strains
  • Thiosemicarbazones*
  • Tissue Distribution
  • Tomography, Emission-Computed*

Substances

  • Copper Radioisotopes
  • Organometallic Compounds
  • Thiosemicarbazones
  • copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex