title: Copper-64-labeled antibodies for PET imaging.
abstract: In the imaging of tumors using radiolabeled monoclonal antibodies, the use of PET gives increased sensitivity over conventional gamma camera imaging techniques. Copper-64, a positron-emitting radionuclide, has been labeled to 1A3, an anticolorectal carcinoma monoclonal antibody, and its fragments 1A3-F(ab')2 utilizing the bifunctional chelate Br-benzyl-TETA. The 64Cu-labeled intact 1A3 and 1A3-F(ab')2 have been evaluated as potential imaging agents for PET. Biodistribution studies of 64Cu-benzyl-TETA-1A3 and 64Cu-benzyl-TETA-1A3-F(ab')2 in tumor-bearing hamsters were compared with those of 111In-Br phi HBED-1A3, 111In-Br phi HBED-1A3-F(ab')2 and 125I-labeled intact 1A3 and 1A3-F(ab')2. Tumor uptake of 64Cu-labeled intact 1A3 and fragments in the hamster model was superior to both 111In- and 125I-labeled intact 1A3 and fragments. Human dosimetry data for 64Cu- and 123I-labeled 1A3 and 1A3-F(ab')2 were calculated from biodistribution data in rats. High kidney uptake of 64Cu-benzyl-TETA-1A3-F(ab')2 precludes clinical study at this time; however, the data shows that 64Cu-benzyl-TETA-1A3 would be suitable for positron tomography imaging of colorectal cancer in patients.
authors.affiliation: Division of Radiation Sciences, Washington University Medical School, St. Louis, Missouri 63110.
authors.forename: C J
authors.initials: CJ
authors.lastname: Anderson
authors.forename: J M
authors.initials: JM
authors.lastname: Connett
authors.forename: S W
authors.initials: SW
authors.lastname: Schwarz
authors.forename: P A
authors.initials: PA
authors.lastname: Rocque
authors.forename: L W
authors.initials: LW
authors.lastname: Guo
authors.forename: G W
authors.initials: GW
authors.lastname: Philpott
authors.forename: K R
authors.initials: KR
authors.lastname: Zinn
authors.forename: C F
authors.initials: CF
authors.lastname: Meares
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D003301:Copper Radioisotopes; D006224:Cricetinae; D004492:Edetic Acid / Q000031:analogs & derivatives; D005260:Female; D006571:Heterocyclic Compounds; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011919:Rats, Inbred Strains; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; C046529:6-(4-bromoacetamidobenzyl)-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid; C042778:N,N'-bis(5-bromo-2-hydroxybenzyl)ethylenediamine diacetic acid; D004492:Edetic Acid