Increasing Reaction Rates of Water-Soluble Porphyrins for ⁶⁴Cu Radiopharmaceutical Labeling

Searching for new compounds and synthetic routes for medical applications is a great challenge for modern chemistry. Porphyrins, natural macrocycles able to tightly bind metal ions, can serve as complexing and delivering agents in nuclear medicine diagnostic imaging utilizing radioactive nuclides of copper with particular emphasis on ⁶⁴Cu. This nuclide can, due to multiple decay modes, serve also as a therapeutic agent. As the complexation reaction of porphyrins suffers from relatively poor kinetics, the aim of this study was to optimize the reaction of copper ions with various water-soluble porphyrins in terms of time and chemical conditions, that would meet pharmaceutical requirements and to develop a method that can be applied for various water-soluble porphyrins. In the first method, reactions were conducted in a presence of a reducing agent (ascorbic acid). Optimal conditions, in which the reaction time was 1 min, comprised borate buffer at pH 9 with a 10-fold excess of ascorbic acid over Cu²⁺. The second approach involved a microwave-assisted synthesis at 140 °C for 1-2 min. The proposed method with ascorbic acid was applied for radiolabeling of porphyrin with ⁶⁴Cu. The complex was then subjected to a purification procedure and the final product was identified using high-performance liquid chromatography with radiometric detection.