Expedient Multi-Step Synthesis of Organometallic Complexes of Tc and Re in High Effective Specific Activity. A New Platform for the Production of Molecular Imaging and Therapy Agents

For over thirty years, instant labeling kits which involve no purification steps have been the only method used to prepare 99mTc radiopharmaceuticals for clinical studies. To address the limitations imposed by instant kits, which is hindering the development of molecularly targeted Tc- and Re-based imaging and therapy agents, a new strategy for the rapid multistep synthesis and purification of organometallic technetium-based molecular probes and corresponding rhenium-based therapeutic analogues was developed. Beginning with MO4− (M = 99mTc, 186/188Re), the carbonyl precursor [M(CO)3(H2O)3]+ was synthesized in 3 min in quantitative yield in a microwave reactor. A dipicolyl ligand was added and the chelate complex was formed in high yield in 2 min using microwave heating at 150 °C. This was followed by a new purification strategy to remove unlabeled ligand which entailed using a copper resin/C18 solid phase extraction protocol giving the desired product in greater than 78% decay corrected yield (dcy). Conve...