Performance of a Zn-62/Cu-62 generator in clinical trials of PET perfusionagent Cu-62-PTSM

The Zn-62/Cu-62 PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing p ractice guidelines. It therefore has the potential to greatly facilitate de velopment of clinically practical PET. We report generator performance in a study in which Cu-62-pyruvaldehyde-bis(n4-methylthiosemicarbazone (PTSM) m yocardial perfusion imaging is compared with Tc-99m-sestamibi in the diagno sis of coronary artery disease. The 62Zn/62Cu generator is an improved Vers ion of a previously reported system that employs automated synthesis of Cu- 62-PTSM. With this approach, the cumbersome step of C-18 purification has b een eliminated. Methods: The Zn-62 (9.3 h half-life) parent isotope is prep ared by proton bombardment of natural copper at 33 MeV. A typical target ir radiated with 37.5 mu A/h is delivered by 12:00 PM on the day it is to be p rocessed. Purified 62Zn obtained from the target is loaded onto the generat or column in 2 mol/L HCl. The generator is eluted using an internal three-c hannel peristaltic pump, which delivers 2.25 mt eluant (1.8 mol/L NaCl, 0.2 mol/L HCl) through the generator column to elute the Cu-62 in 40 s. The sa me pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) an d 1 mt ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum in to a 35-cc syringe preloaded with 28 mt sterile water. This solution is tho roughly mixed by agitation of the syringe and injected as a bolus through a 0.2 mu m filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight de livery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. Results: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase ill Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7 +/- 0.2 GBq (46.7 +/- 5.6 mCi), and yield w as 72% +/- 16%. Breakthrough of 62Zn was undetectable by high-purity german ium spectroscopy for all units. Radiochemical purity was 95.4% +/- 2.4%. Vo lume delivered, pH, sterility, and bacterial endotoxin tests yielded passin g results on all generators. The entire process of generator production, fr om target receipt to generator shipment, took less than 6 h and cost approx imately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 Cu-62-PTSM doses, with a mean injected activ ity of 0.8 +/- 0.2 GBq (20.5 +/- 5.3 mCi) with no adverse side effects. Con clusion: Results of this work confirm that the Zn-62/Cu-62 generator is an easily produced, transportable, and inexpensive source of PET radiopharmace uticals, which can expand the field of clinical PET imaging by providing ra diopharmaceuticals to sites not associated with cyclotrons.