New anti-Cu-TETA and anti-Y-DOTA monoclonal antibodies for potential use in the pre-targeted delivery of radiopharmaceuticals to tumor.
Monoclonal antibodies were raised against yttrium(III)-1, 4, 7, 10-tetraazacyclododecane-N,N',N''N'''--tetraacetic acid (Y-DOTA) and copper(II)-1, 4, 8, 11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (Cu-TETA). Four hybridomas with high Y-DOTA binding activity and one hybridoma with Cu-TETA activity were selected. MAbs were purified from mouse ascites by Protein A affinity chromatography and characterized. Affinity constants were determined by equilibrium dialysis and the highest affinity Y-DOTA MAb (K(aff) = 1.9 x 10(8) M(-1)) was further characterized by competitive ELISA. Gd-DOTA competed as well as Y-DOTA, whereas In-DOTA required 740x higher concentrations for 50% inhibition of this Y-DOTA MAb binding to human serum albumin-Y-DOTA-coated microtiter plates. These anti-metal chelate MAbs have potential use as vehicles for the pretargeted delivery of radiometal chelates to tumors.
Feng
X
X
Division of Hematology/Oncology, University of California Davis Medical Center, Sacramento 95816, USA.
Pak
R H
RH
Kroger
L A
LA
Moran
J K
JK
DeNardo
D G
DG
Meares
C F
CF
DeNardo
G L
GL
DeNardo
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D000915:Antibody Affinity; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D006571:Heterocyclic Compounds / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000276:immunology*; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012680:Sensitivity and Specificity
D000911:Antibodies, Monoclonal; D006241:Haptens; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C113624:copper(II)-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid; C113625:yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid