Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II): synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion.
Generator produced positron-emitting radionuclides could potentially expand the application of positron emission tomography (PET) to centers that do not have access to a local cyclotron. The zinc-62/copper-62 radionuclide generator system could serve as a source of positron-emitting copper-62 (62Cu) (t1/2 = 9.74 min) for physiologic imaging. Accordingly, we have prepared zinc-62/copper-62 generators capable of high output (greater than 300 mCi) and used the no-carrier-added eluate in a rapid high yield synthesis of [62Cu] Cu(PTSM) that provides the radiopharmaceutical in a form suitable for intravenous injection (where Cu(PTSM) = pyruvaldehyde bis(N4-methylthiosemicarbazonato) copper(II]. We then demonstrated in pilot studies that [62Cu]Cu(PTSM) provides high quality brain and heart images with PET, accurately delineating cerebral and myocardial perfusion in both experimental animals and in humans (corroborating results of previous experimental studies utilizing longer-lived copper isotopes). The results of this work demonstrate that 62Cu can be conveniently obtained from high-level generators and, when used to label Cu(PTSM), provides a generator-produced radiopharmaceutical capable of providing estimates of cerebral and myocardial perfusion independent of cyclotron-produced radionuclides.
Green
M A
MA
Dept. of Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Purdue University, West Lafayette, IN 47097.
Mathias
C J
CJ
Welch
M J
MJ
McGuire
A H
AH
Perry
D
D
Fernandez-Rubio
F
F
Perlmutter
J S
JS
Raichle
M E
ME
Bergmann
S R
SR
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation; D003301:Copper Radioisotopes; D003326:Coronary Circulation; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008254:Macaca nemestrina; D008297:Male; D009942:Organometallic Compounds / Q000138:chemical synthesis; D011876:Radionuclide Generators; D013882:Thiosemicarbazones / Q000138:chemical synthesis; D014055:Tomography, Emission-Computed
D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C063293:copper (II) pyruvaldehyde bis(N(4)-dimethylthiosemicarbazone)