Copper(II) bis(thiosemicarbazone) complexes as potential tracers for evaluation of cerebral and myocardial blood flow with PET.
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.
Green
M A
MA
Department of Radiology, University of Minnesota, Minneapolis.
Klippenstein
D L
DL
Tennison
J R
JR
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002560:Cerebrovascular Circulation; D003301:Copper Radioisotopes; D003326:Coronary Circulation; D005849:Gerbillinae; D006321:Heart / Q000000981:diagnostic imaging*; D008252:Macaca fascicularis; D008297:Male; D009942:Organometallic Compounds; D011876:Radionuclide Generators; D051381:Rats; D011919:Rats, Inbred Strains; D013882:Thiosemicarbazones; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex