Novel radiolabeled antibody conjugates

Abstract

This article reviews the development of radioimmunoconjugates as a new class of cancer therapeutics. Numerous conjugates involving different antigen targets, antibody forms, radionuclides and methods of radiochemistry have been studied in the half-century since radioactive antibodies were first used in model systems to selectively target radiation to tumors. Whereas directly conjugated antibodies, fragments and subfragments have shown promise preclinically, the same approaches have not gained success in patients except in radiosensitive hematological neoplasms, or in settings involving minimal or locoregional disease. The separation of tumor targeting from the delivery of the therapeutic radionuclide in a multistep process called pretargeting has the potential to overcome many of the limitations of conventional, or onestep, radioimmunotherapy, with initial preclinical and clinical data showing increased sensitivity, specificity and higher radiation doses delivered. Our particular focus in pretargeting is the use of bispecific, trimeric (three Fab 0 s) constructs made by a new antibody engineering method termed 'dock-and-lock.'

Renaissance of nuclear medicine through green nanotechnology: functionalized radioactive gold nanoparticles in cancer therapy—my journey from chemistry to saving human lives

“…The larger size of monoclonal antibodies (or of even the smaller fragments) is a major barrier to achieve transvascular passage into tumors. Low tumor permeation by the selected large molecules, low tumor uptake due to active or passive targeting and undesirable pharmacokinetics have precluded the administration of radio immunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of radioimmunotherapy (RIT) [29][30][31]. One of the most common issues limiting the effectiveness of antibody labeled targeted radiopharmaceuticals is believed to be low tumor permeation due to the large size of targeting vectors (*150 kDa).…”

Selection and Evaluation of Human Recombinant Antibodies against ErbB2 Antigen for Breast Cancer Immunotherapy

“…A number of antitumor scFvs, alone or in conjugation with toxins, have been introduced in clinical trials. Bispecific, diabody, tribody, and tetrabody scFvs are other forms of scFvs, which have great potential for efficient tumor targeting (30,31).…”

Radiofrequency Ablation Before Intratumoral Injection of 131I-chTNT Improves the Tumor-to-Normal Tissue Ratio in Solid VX2 Tumor

“…2,8 At present, a number of MABs have been developed for RIT, and several isotopes have been successfully tested and applied to antitumor therapy. 2,8,12,26,27 In this study, the radioactive iodine ( 131 I) labeled MAB (-chTNT), as RIT agents, was applied to treat the solid tumor (VX 2 tumor). 131 I is a mixed b-c emitter with a half-life of 8 days.…”