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Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies

Robert M. Sharkey, PhD;1 and David M. Goldenberg, ScD, MD1

1 Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey



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FIGURE 1. Comparison of administration conditions for 131I-tositumomab) and 90Y-ibritumomab tiuxetan. Reprinted with permission from Goldenberg, DM. Therapeutic use of radiolabeled antibodies: hematopoietic tumors. In: Ell PJ, Gambhir SS, eds. Nuclear Medicine in Clinical Diagnosis and Treatment. 3rd ed. London, UK: Churchill Livingstone; 2004:428–434.

 


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FIGURE 2. Schematic representation of various forms of antibody fragments prepared by enzymatic digestion or molecular engineering. The most commonly used form of antibody, IgG, has been radiolabeled by conjugating directly to the protein (e.g., radioiodination of tyrosine) or radiolabeling a coupled chelator. Chelators have been coupled directly to the protein or to the carbohydrates that reside on the Fc-portion of the molecule. Single chains are formed by linking the variable light (VL) and variable heavy (VH) chains with amino acid (AA) linker. Diabodies, triabodies, and even tetrabodies are formed spontaneously when smaller length AA chains are used to hold the VH and VL units together. Recombinant bispecific diabodies and other bispecific constructs can be prepared by pairing VH and VL of 2 antibodies with different specificities.

 


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FIGURE 3. The next generation of radionuclide targeting; examples of pretargeting approaches: (A) Two-step streptavidin IgG/radiolabeled biotin procedure (177,191). (B) Three-step biotinylated IgG/radiolabeled biotin pretargeting procedure (160,161). (C) Bispecific antibody pretargeting procedure (164). (D) Oligonuclide pretargeting procedure (165–167).

 





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