Copper and diphosphine complexes: new radiopharmaceuticals for PET imaging of the myocardium.

Aim: To realize a new kit for PET of easy and fast preparation to be used for the imaging of myocardial ischemia, infarcted myocardium, and evaluation of ventricular function. Materials and methods: non radioactive complexes were synthesised for a fully characterised standards to identify radiotracers by TLC.64Cu was produced with an IBA 18 MeV cyclone, and the radiosynthesis were tested with three different phospynes (P1,P2,P3) adding 64CuCl2 (10-50 microliter) solution to P1.P2,P3 (1microliter) for 1 minute at room temperature. The lipophilicity was measured using the octanol-water partition coefficient, and the serum stability was executed with a sample of 64Cu complex (1MBq) added to 5ml of human serum. The animal studies were executed with YAP-PET micropet, working with a total of twenty male rats of 8-10 weeks of age and weighing about 250. The biodistribution was performed with a well-type counter and radioactivity concentration expressed as % ID per gram of tissue. Results: Different radiochemical syntheses with 64Cu show diphosphine functioning as reducing agent as well as chelator, and for practical purposes all the reactions may be regarded as instantaneous and eliminating any need for purification steps. Serum stability measurements show that complexes survive largely intact over the likely time scale of clinical PET imaging. The animal biodistribution experiments show that the compounds are quickly cleared from the blood, largely by the kidneys and by the liver. Conclusions: Diphosphine ligands offer a good starter for development of new radiopharmaceuticals with copper radioisotopes dedicated for PET, that could be used both to continuous cardiac monitoring and emergency cardiac treatment.