N,N'-bis(2-hydroxybenzyl)-1-(4-bromoacetamidobenzyl)-1,2 -ethylenediamine-N,N'-diacetic acid: a new bifunctional chelate for radiolabeling antibodies. 1990

C J Mathias, and Y Z Sun, and M J Welch, and J M Connett, and G W Philpott, and A E Martell
Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, Missouri 63110.

N,N'-Bis(2-hydroxybenzyl)-1-(4-bromoacetamidobenzyl)-1,2 -ethylenediamine-N,N'-diacetic acid (Br phi HBED) was synthesized to bind trivalent metals with high stability constants and to bifunctionally link the radiometal with antibodies (Ab). This ligand has advantages over our previously reported N-(2-hydroxy-3,5-dimethylbenzyl)-N'-(2-hydroxy-5- bromoacetamidobenzyl)ethylenediamine-N,N'-diacetic acid (BrMe2HBED). Br phi HBED has the protein coupling group BrCH2CONH removed from the sterically hindered ring position with the addition of a benzyl group in the linker arm; this provides further distance between the protein and the chelate. We have also observed that the chelate was more stable than BrMe2HBED, so it can be stored longer without loss of observed chemical properties. The improved chelate design allows for more rapid radiolabeling with [111In]indium citrate (1 h at room temperature) with higher radiochemical yields. Br phi HBED was conjugated with an anticolorectal carcinoma monoclonal antibody (1A3) where radiolabeling yields of 75-90% were obtained and the antibody retained its immunoreactivity (ca. 90%) under all labeling conditions studied. Biodistribution studies in a hamster transplanted tumor (GW39) model demonstrated a high tumor uptake when compared to those of 125I-1A3 or 111In-DTPA cyclic anhydride-1A3. Blood clearance of 111In-Br phi HBED-1A3 was rapid and combined with its high target uptake has higher target to nontarget ratios in vivo at various time intervals when compared with that of 1A3 radiolabeled with either 111In-DTPA cyclic anhydride or 125I.

UI MeSH Term Description Entries
D007205 Indium Radioisotopes Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes. Radioisotopes, Indium
D007553 Isotope Labeling Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms. Isotope Labeling, Stable,Isotope-Coded Affinity Tagging,Isotopically-Coded Affinity Tagging,Affinity Tagging, Isotope-Coded,Affinity Tagging, Isotopically-Coded,Isotope Coded Affinity Tagging,Labeling, Isotope,Labeling, Stable Isotope,Stable Isotope Labeling,Tagging, Isotope-Coded Affinity,Tagging, Isotopically-Coded Affinity
D008297 Male Males
D008647 Mesocricetus A genus in the order Rodentia and family Cricetidae. One species, Mesocricetus auratus or golden hamster is widely used in biomedical research. Hamsters, Golden,Hamsters, Golden Syrian,Hamsters, Syrian,Mesocricetus auratus,Syrian Golden Hamster,Syrian Hamster,Golden Hamster,Golden Hamster, Syrian,Golden Hamsters,Golden Syrian Hamsters,Hamster, Golden,Hamster, Syrian,Hamster, Syrian Golden,Syrian Hamsters
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D002614 Chelating Agents Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D004492 Edetic Acid A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive. EDTA,Edathamil,Edetates,Ethylenediaminetetraacetic Acid,Tetracemate,Calcium Disodium Edetate,Calcium Disodium Versenate,Calcium Tetacine,Chelaton 3,Chromium EDTA,Copper EDTA,Coprin,Dicobalt EDTA,Disodium Calcitetracemate,Disodium EDTA,Disodium Ethylene Dinitrilotetraacetate,Distannous EDTA,Edetate Disodium Calcium,Edetic Acid, Calcium Salt,Edetic Acid, Calcium, Sodium Salt,Edetic Acid, Chromium Salt,Edetic Acid, Dipotassium Salt,Edetic Acid, Disodium Salt,Edetic Acid, Disodium Salt, Dihydrate,Edetic Acid, Disodium, Magnesium Salt,Edetic Acid, Disodium, Monopotassium Salt,Edetic Acid, Magnesium Salt,Edetic Acid, Monopotassium Salt,Edetic Acid, Monosodium Salt,Edetic Acid, Potassium Salt,Edetic Acid, Sodium Salt,Ethylene Dinitrilotetraacetate,Ethylenedinitrilotetraacetic Acid,Gallium EDTA,Magnesium Disodium EDTA,N,N'-1,2-Ethanediylbis(N-(carboxymethyl)glycine),Potassium EDTA,Stannous EDTA,Versenate,Versene,Acid, Edetic,Acid, Ethylenediaminetetraacetic,Acid, Ethylenedinitrilotetraacetic,Calcitetracemate, Disodium,Dinitrilotetraacetate, Disodium Ethylene,Dinitrilotetraacetate, Ethylene,Disodium Versenate, Calcium,EDTA, Chromium,EDTA, Copper,EDTA, Dicobalt,EDTA, Disodium,EDTA, Distannous,EDTA, Gallium,EDTA, Magnesium Disodium,EDTA, Potassium,EDTA, Stannous,Edetate, Calcium Disodium,Ethylene Dinitrilotetraacetate, Disodium,Tetacine, Calcium,Versenate, Calcium Disodium
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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