Evaluation of copper-labeled bifunctional chelate-albumin conjugates for blood pool imaging

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 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 ⁶²Cu and administered to a dog for blood-pool imaging using PET. Images were nearly identical to an image taken after administration of C¹⁵O. 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 C¹⁵O for PET facilities without cyclotrons.