Evaluation of copper-labeled bifunctional chelate-albumin conjugates for blood pool imaging.
62Cu(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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Mallinckrodt Institute of Radiology, Washington University Medical School, St Louis, MO 63110.
C J
CJ
Anderson
P A
PA
Rocque
C J
CJ
Weinheimer
M J
MJ
Welch
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics; D003300:Copper / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D003301:Copper Radioisotopes; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000493:pharmacokinetics; D003952:Diagnostic Imaging / Q000379:methods; D004285:Dogs; D004355:Drug Stability; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006571:Heterocyclic Compounds / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D009942:Organometallic Compounds / Q000097:blood* / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D000075462:Serum Albumin, Human; D013882:Thiosemicarbazones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002614:Chelating Agents; D003301:Copper Radioisotopes; D003432:Cross-Linking Reagents; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D012709:Serum Albumin; D013882:Thiosemicarbazones; C067800:copper acetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid-serum albumin; D003300:Copper; D004369:Pentetic Acid; C049200:4-carboxyethylphenylglyoxal-bis(N-methylthiosemicarbazone); D000075462:Serum Albumin, Human