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2016 JUL 16 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Researchers detail new data in Lymphoproliferative Disorders. According to news reporting out [...]

Background. Studies on radiolabeled monoclonal antibodies (MoAb) have dealt mainly with single antibodies. However, major differences may exist among different radiolabeled MoAb that bind to the same antigen and between switch variants of the same antibody. This study evaluates and compares a series of radiolabeled MoAb of different specificities, subclasses, and isotypes applicable in treatment of patients with B cell malignancies. Methods. MoAb were iodinated with iodogen. Immunoreactivity was determined in cell binding assays. Scatchard analyses were performed to determine association constants of radiolabeled Moab and to measure antigen density on malignant B cells in various differentiation stages. The fate of the MoAb after antigen binding in vitro was studied by modulation and internalization experiments. Results. All MoAb tested could be iodinated efficiently and displayed association constants of 0.9 X [10.sup.9] [M.sup.-1] or higher. Immunoreactivity of radiolabeled MoAb ranged from 62-79%, except for the immunoglobulin (Ig)-M MoAb CLB-MD20.2, which had an immunoreactivity of 43%. The highest number of binding sites was detected for the CD20 MoAb (12 X [10.sup.3] - 355 X [10.sup.3]), whereas the expression of antigens recognized by the CD22 MoAb was lowest on all cell types tested (4 X [10.sup.3] - 26 X [10.sup.3]). The MoAb CD19 and CD22 both induced modulation, whereas the CD20 MoAb did not. Modulation induced by the CD19 MoAb was caused by internalization. The rate of internalization was isotype-dependent and, for CD19-IgG1, partly mediated by Fc [gamma] ReceptorII. Conclusions. Radiolabeled B cell MoAb tested in this study are promising for use in radioimmunotherapy. For therapy with the radioisotope iodine-131, the IgG2a and IgG2b CD19 MoAb are more suitable than CD19-IgG1, because of their slower modulation and internalization rate.

Background. Antibody sulfhydryl groups can act aseffective carriers of reduced technetium and rheniumspecies for radioimmunodetection and radioimmunotherapy.Methods. Intact immunoglobulin G and fragmentswere labeled with the isotopes and examined in vitro andin vivo.Results. Technetium bound to intact immunoglobulinG was found to be the most stable species in vitro, butin vivo, clearances of technetium and rhenium bound tointact antibody were similar. Serum clearances werefaster than those seen for the corresponding radioiodinated antibodies. In vivo clearance rates of the radiolabeledfragments were similar, with kidney uptake andretention seen. Rhenium-labeled antibodies, despite agreater tendency toward in vitro reoxidation than technetium-labeled antibodies, did not show enhanced kidneyclearance in animal models. Rhenium-188 and technetium-99mwere obtained from similar generator systemsin carrier-free form. Using rhenium-188 spikedwith cold rhenium, it was determined that approximatelyone rhenium atom per molecule of antibody canbe conjugated directly. Rhenium-186 also was coupled atalmost a 1:1 ratio to antibody.Conclusions. Only radiolysis concerns will limit theamount of rhenium-188 conjugated to antibody. Largedoses of antibody will be necessary to deliver rheniumat186 this isotope's currently available specific activity.Otherwise, higher specific activity rhenium-186, and/orgreater loading capacity of rhenium-186 onto antibody,will be needed to generate the type of product that will be usable at a clinical dose of several hundred millicuries.

Background. The development of new bifunctional chelating agents for the labeling of monoclonal antibodies with radiometals is a desirable goal in the area of radioimmunodetection and radioimmunotherapy of cancer. The authors have developed a new N3S-ligand, N-(S-acetylmercaptoacetyl) (p-NCS)phenylalanylglycylglycine ethyl ester (MAIPGG) for technetium-99m ([sup.99m.Tc]) or rhenium-186 ([sup.186.Re]) labeling of monoclonal antibody D612 reactive with human colon cancer. The biodistribution of [sup.99m.Tc/186Re]-MAIPGG-D612 conjugates was studied in nude mice bearing human colon cancer xenografts. Methods. MAIPGG was synthesized from Boc-p-nitrophenylalanine and was coupled to antibody D612, and the conjugate was labeled with [sup.99m.]Tc using a Glucoscan kit (DuPont, North Billerico, MA) as the reducing system. [sup.186.Re]-MAIPGG-D612 was prepared by radiolabeling MAIPGG with [sup.186.Re], with sodium citrate/SnCl2, used as a reducing system, after which the raiolabeled MAIPGG was coupled to monoclonal antibody D612. The biodistribution of these radioimmunoconjugates in athymic nude mice bearing LS174T human colon cancer xenografts was studied. Results. The cold precursor MAIPGG was prepared easily from Boc-p-nitro phenylaianine with an overall yield of 12-15%, which, when coupled to monoclonal antibody D612, did not affect its binding activity to LS174T cells in vitro. The biodistribution and imaging results demonstrated that these radioimmunoconjugates localized preferentially in tumor. Conclusions. These preliminary results suggest that MAIPGG may be useful for the radiolabeling of a variety of monoclonal antibodies with [sup.99m.Tc] or [sup.186.Re,] which then can be used for radioimmunodetection and radioimmunotherapy of cancer.

Seventeen years after the development of hybridoma technology, the clinical utility of radioimmunodetection of solid tumors using monoclonal antibody-based imaging agents has been definitively established. As expected, these first immunoscintigraphy agents demonstrate certain limitations (most notably, suboptimal tumor-to-background radiolocalization ratios and immunogenicity), suggesting that the full potential of this technology has not been realized. This article reviews research strategies for optimizing the imaging performance of radiolabeled monoclonal antibodies. Promising approaches include the development of humanized tumor-targeting vehicles, improved chelator technology to link the antibody and the radioisotope, the use of smaller immunoreactive targeting agents, modifications of the tumor or host determinants of antibody biodistribution, regional delivery of immunoscintigraphic agents, use of antibody 'cocktails,' advances in image acquisition technology. The successful application of these strategies should lead to improved agents for tumor radioimmunodetection. The results of these research efforts should be useful in developing radiolabeled monoclonal antibody-based agents for solid tumor therapy.