Abstract
62Cu ( T 1 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 diethylenetriaminepentaacetic 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 67Cu. The labeling efficiency of 67Cu-DTS-HSA was > 90%, whereas the labeling yields of 67Cu-DTPA-HSA and 67Cu-benzyl-TETA-HSA were less than 70%. Blood clearance and biodistribution of these three 67Cu-labeled conjugates were determined in rats. Of the three 67Cu-labeled bifunctional chelate-HSA conjugates, 67Cu-benzyl-TETA-HSA remained in the blood pool the longest, achieving stable blood levels at times longer than 24 h post-injection. The 67Cu radioactivity cleared the blood within 60 min post-injection of 67Cu-DTS-HSA, and within 10 min after administration of 67Cu-DTPA-HSA, indicating the dissociation of Cu 2+ 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 62Cu and administered to a dog for blood-pool imaging using PET. Images were nearly identical to an image taken after administration of C 15O. Because of the high labeling efficiency, DTS-HSA can be labeled with 62Cu without purification, making it more practical than 62Cu-benzyl-TETA-HSA as a blood-pool imaging agent. Generator-produced 62Cu-DTS-HSA should be a viable alternative blood pool agent to cyclotronproduced C 15O for PET facilities without cyclotrons.
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