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Copper-62-Labeled Pyruvaldehyde Bis(N⁴-methylthiosemicarbazonato)copper(II): Synthesis and Evaluation as a Positron Emission Tomography Tracer for Cerebral and Myocardial Perfusion

Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Purdue University, West Lafayette, Indiana
Division of Radiation Sciences, Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri
Cardiovascular Division, Department of Internal Medicine, Washington University, St. Louis, Missouri
Radiochemistry Department, Maryland Heights Cyclotron Facility, Mallinckrodt Medical, Inc., Maryland Heights, Missouri

Correspondence: For reprints contact: Mark A. Green, Dept. of Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Purdue University, West Lafayette, IN 47097.

ABSTRACT

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 = 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.

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