Synthesis and formulation of [64Cu]Cu-PTSM for PET perfusion imaging in small animal models

Purpose: The [Cu-64]Cu-PTSM radiopharmaceutical, pyruvaldehyde bis(N-4-methylthiosemicarbazonato)copper (II), is suitable for use in microPET and autoradiographic imaging to assess regional tissue perfusion in small animal models. We report here an approach to synthesis and formulation of the [Cu-64]Cu-PTSM radiopharmaceutical at the high concentrations required for use in imaging with rodent models of human disease. Methods: The [Cu-64]Cu-PTSM radiopharmaceutical was prepared at small volumes by addition of the H2PTSM ligand to acetate-buffered [Cu-64]copper chloride, followed by solid phase extraction to isolate and purify the product, which was then recovered and formulated in 2-mL normal saline containing 5% ethanol and 5% propylene glycol. Results. The [Cu-64]Cu-PTSM radiopharmaceutical has been produced over the range of 0.41-1.85 GBq (11-50 mCi) [Cu-64]Cu-PTSM in the 2.0-mL final product volume. Radiochemical purity of the [Cu-64]Cu-PTSM radiopharmaceutical product averaged 99.8 +/- 0.4% (n = 64), with the final formulated product produced at an 83 +/- 5% radiochemical yield. Conclusions: The approach to [Cu-64]Cu-PTSM synthesis and formulation has proven to be reliable and robust, supporting radiopharmaceutical delivery at the high concentrations required for PET studies in mouse and other rodent models.