In vivo comparison of copper blood-pool agents: potential radiopharmaceuticals for use with copper-62.
Two techniques for labeling of albumin with copper-67 (67Cu) and 62Cu were investigated; one using the native Cu(II) binding site of the protein and the other employing a bifunctional chelate, 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane- N,N'N",N"'-tetraacetic acid (Br-benzyl-TETA or BAT), conjugated to the protein. Rat biodistribution experiments with 67Cu demonstrated retention of i.v. 67Cu-benzyl-TETA-albumin in the blood pool identical to co-injected 125I-albumin. By contrast, i.v. administration of either [67Cu]-Cu-acetate or [67Cu]-Cu-acetate pre-mixed with albumin results in relatively rapid clearance of blood-pool radioactivity as the tracer is excreted into the urine. The 62Cu-benzyl-TETA-albumin radiopharmaceutical was obtained in ca. 17% radiochemical yield (end of synthesis, without decay correction) following a procedure that can be completed in 15-18 min. In PET experiments with a baboon, myocardial blood volume images with 62Cu-benzyl-TETA-albumin were identical to those obtained with C15O. Use of the 62Cu-benzyl-TETA-albumin image for blood-pool subtraction of a 62Cu-PTSM myocardial perfusion image is illustrated. Copper-62-benzyl-TETA-HSA should be a useful, generator-produced radiotracer for the detection of the vascular pool at PET facilities without cyclotrons.
Mathias
C J
CJ
Edward Mallinckrodt Institute of Radiology, Department of Internal Medicine, Washington School of Medicine, St. Louis, Missouri.
Welch
M J
MJ
Green
M A
MA
Diril
H
H
Meares
C F
CF
Gropler
R J
RJ
Bergmann
S R
SR
D000818:Animals; D001811:Blood Volume Determination / Q000379:methods*; D003300:Copper / Q000493:pharmacokinetics*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D010215:Papio; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000493:pharmacokinetics*; D000075462:Serum Albumin, Human; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D012709:Serum Albumin; C067800:copper acetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid-serum albumin; D003300:Copper; D000075462:Serum Albumin, Human