United Kingdom (UK)
Recombinant monoclonal antibody to DOTA (metal-bound). Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the hybridoma 2D12.5.
Alternative Name(s) of Target: Tetraxetan; dodecane tetra acetic acid; CHEBI:61028; Yttrium(III) labeled DOTA; Y-DOTA; Yttrium-1 4 7 10-tetraazacyclododecanetetraacetic acid; metal-DOTA
Immunogen: The original antibody was generated by immunizing BALB/c mice with KLH-21T-BAD-Y(III).
Specificity: This antibody binds metal bound DOTA (Tetraxetan) and also shows binding affinity for Yttrium(III) labeled DOTA, (S) nitro benzyl-DOTA chelates and Janus-DOTA (a bivalent form of DOTA). DOTA is a chelating agent which can be labelled with radioactive yttrium ion and even conjugated with monoclonal antibodies for radioimmunotherapy.
Application Notes: The original mouse IgG1 antibody binds DOTA chelates of all the rare earths with approximately Kd ≈ 10(-8) M, making it useful for the capture of probe molecules with a variety of properties (PMID: 15546206). The original IgG1 version of this antibody was used in the pretargeting for radioimmunotherapy in BALB/c mice with KHJJ tumors (PMID: 7954426). In vivo clearance studies have demonstrated that 74-96% of 2D12.5 bound to metal chelates is present 24 hours after administration of the bound complex (US7528235). An engineered version of this antibody with a single cysteine residue at position 54, 55 or 56 of the heavy chain, a site proximal to the protein's binding site, enables formation of weakly electrophilic metal complexes of (S)-2-(4-acrylamidobenzyl)-DOTA (AABD) that may bind and form permanent linkages (PMID: 15546206; 15546207). The heavy chain G54C mutant had a small set of electrophilic ligands, differences in reactivity indicated that the substituents near the electrophilic atom can be important determinants of permanent binding (PMID: 15546207).
Antibody first published in:
Goodwin et al. Pharmacokinetics of pretargeted monoclonal antibody 2D12.5 and 88Y-Janus-2-(p-nitro benzyl)-1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) in BALB/c mice with KHJJ mouse adenocarcinoma: a model for 90Y radioimmunotherapy. Cancer Res. 1994 Nov 15;54(22):5937-46. PMID:7954426
Note on publication:
Describes the pretargeting and pharmacokinetics of antibody 2D12.5 and DOTA for radioimmunotherapy in mouse models.