EVALUATION OF COPPER-LABELED BIFUNCTIONAL CHELATE ALBUMIN CONJUGATES FOR BLOOD POOL IMAGING

Cu-62 (T1/2 = 9.8 min) is a generator-produced positron-emitting radionuclide with a half-life amenable to blood-pool imaging with PET. Three bifunctional chelates [cyclic anhydride of diethylenetriamine-pentaacetic acid (cDTPAA), 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N',N',N'''-tetraacetic acid (BAT), and p-carboxyethylphenylglyoxal-bis-(4N-methyl-thiosemicarbazone (CE-DTS)] were conjugated to HSA and labeled with Cu-67. The labeling efficiency of Cu-67-DTS-HSA was > 90%, whereas the labeling yields of Cu-67-DTPA-HSA and Cu-67-benzyl-TETA-HSA were less than 70%. Blood clearance and biodistribution of these three Cu-67-labeled conjugates were determined in rats. Of the three Cu-67-labeled bifunctional chelate-HSA conjugates, Cu-67-benzyl-TETA-HSA remained in the blood pool the longest, achieving stable blood levels at times longer than 24 h post-injection. The Cu-67 radioactivity cleared the blood within 60 min post-injection of Cu-67-DTS-HSA, and within 10 min after administration of Cu-67-DTPA-HSA, indicating the dissociation of Cu2+ from these conjugates. Copper-labeled DTS-HSA achieved stable blood concentrations for at least 30 min post-injection and was therefore evaluated as a vascular imaging agent. DTS-HSA and benzyl-TETA-HSA were labeled with Cu-62 and administered to a dog for blood-pool imaging using PET. Images were nearly identical to an image taken after administration of (CO)-O-15. Because of the high labeling efficiency, DTS-HSA can be labeled with Cu-62 without purification, making it more practical than Cu-62-benzyl-TETA-HSA as a blood-pool imaging agent. Generator-produced Cu-62-DTS-HSA should be a viable alternative blood pool agent to cyclotron-produced (CO)-O-15 for PET facilities without cyclotrons.