[Tc]1,4,7,10-tetraazacyclododecane--tetraacetic acid-Phe-Lys-histamine-succinyl-Gly-D-Tyr-Lys- histamine-succinyl-Gly-thiosemicarbazonyl-glyoxyl-cysteine

Radioimmunotherapy is one of the choices available for the treatment of cancer, but this technique is not entirely successful because the antibodies (Abs) used to target the cancers are not very effective against solid tumors. This is primarily because the solid tumors have a low radiosensitivity and the Abs cannot be used to deliver a very high dose of radiation (1). The radionuclides are delivered to the tumors either by directly binding the radionuclide to the Ab that is targeted to a cellular antigen or the tumor cells are first pretargeted with an Ab and then exposed to a suitable ligand that carries the radionuclide for binding to the Ab. Use of Ab bound radioactivity usually results in hematological dose-limiting toxicity because the Ab is cleared very slowly from the blood circulation (2). Some investigators envisioned retargeting the tumors with an Ab followed by an infusion of radioactivity linked to a suitable ligand that rapidly clears from the blood and binds to the Ab would perhaps alleviate the hematological toxicity observed with radiolabeled Abs. Although there are several methods available to pretarget tumors, a common approach is to use bispecific Abs (bsAbs) - these Abs are usually genetically engineered and can bind to two distinct ligands with great specificity, inconjunction with a radiolabeled small molecule such as a hapten (3). Pretargeting with bsAbs for the treatment of tumors is under evaluation in several clinical trials approved by the United States Food and Drug Administration. Sharkey et. al. have evaluated the use of a bispecific monoclonal antibody (bsMoAb) that is divalent for the carcinoembryonic antigen (CEA) and monovalent for anti-histamine-succinyl-glycine (HSG) for the molecular imaging of metastatic human colonic carcinoma in a mouse model (4). The structure of this bsMoAb (designated as TF2) was described by Goldenberg et. al (3). Briefly, the bsMoAb consists of three F(ab) fragments. Two of the fragments were specific for human CEA and the third fragment had binding specificity for HSG. A divalent HSG peptide labeled with radioactive 99m technetium ( Tc) was used for the imaging of tumors that bound the bsMoAb. Data obtained from the pretargeting study was compared to results obtained with radioactive fluorine (F) labeled fluorodeoxyglucose ([F]FDG), the HSG peptide alone or an irrelevant anti-CD22 bsMoAb.