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) (t( 1/2 ) = 9.74 min) for physiologic imaging. Accordingly, we have prepared zinc-62/copper-62 generators capable of high output (>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.