Preparation of [64Cu]Cu–NOTA complex as a potential renal PET imaging agent using 64Cu produced via the direct activation route

Abstract

Abstract Glomerular filtration rate (GFR) could be determined more accurately using renal positron emission tomography (PET) than conventional gamma imaging. Copper-64 [T ½ = 12.7 h, E β+ (max) = 653 keV, β+ branching ratio = 17.8 %, 1346 keV γ-photon (0.54 %), EC (43.8 %), β− emission (38.4 %)] in the form of its hydrophilic complex with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) is proposed as a potent formulation for renal PET imaging. A lyophilized kit was developed for formulation of ∼370 MBq dose of [64Cu]Cu–NOTA complex in a facile single step process using 64Cu produced by thermal neutron activation in a research reactor. The complex could be synthesized with >99 % yield and retained its integrity even when challenged by apoferritin. The rapid accumulation of [64Cu]Cu–NOTA in the kidney and clearance through urinary path was demonstrated using PET/CT imaging and ex vivo biodistribution study carried out in healthy Wistar rats to elucidate its effectiveness as a renal PET-imaging agent.