Radiopharmaceuticals for imaging chronic lymphocytic inflammation

Malviya, Gaurav; Vries, Erik F. J. de; Dierckx, Rudi; Signore, Alberto

doi:10.1590/s1516-89132007000600002

Cited by 8 publications

(7 citation statements)

References 66 publications

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“…Our group recently radiolabelled visilizumab (Nuvion), with 99m-technetium by using a hetero bifunctional linker SHNH/S-HYNIC (succinimidyl-6-hydrazinonicotinate hydrochloride) with a high labelling efficiency (>90%) and high specific activity (9,990–11,100 MBq/mg). The in vitro and in vivo results in the animal model demonstrated very potential results for the targeting of CD3 positive human lymphocytes [ 85 , 86 ]. The effectiveness of 99m Tc-labelled visilizumab, however, has yet to be checked in humans, but this new radiopharmaceutical may provide a useful tool for in vivo imaging of several immune-mediated inflammations as well as a rationale for therapy with unlabelled anti-CD3 mAb and follow-up of the disease activity.…”

Section: New Imaging Strategies As a Guide To Molecular Therapiesmentioning

confidence: 99%

Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

Malviya

Conti

Chianelli

et al. 2009

Eur J Nucl Med Mol Imaging

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The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99mTc or 111In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform ‘evidence-based biological therapy’ of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and follow-up.

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Section: New Imaging Strategies As a Guide To Molecular Therapiesmentioning

confidence: 99%

Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

Malviya

Conti

Chianelli

et al. 2009

Eur J Nucl Med Mol Imaging

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“…Several studies demonstrated that the 99m Tc-human polyclonal immunoglobulin could be used not only for the assessment of disease activity but also as an effective prognostic tool for the inflammation-mediated disorders (19,20). But data in the literature showed that IgG also accumulates in the inflammatory foci by nonspecific extravasation facilitated by locally enhanced vascular permeability (21). Therefore, there is a need for more specific and sensitive radiopharmaceuticals for the diagnosis of inflammation, possibly targeting different molecules such as lymphocyte activation markers, soluble cytokines, endothelial activation markers, or other cell receptors.…”

Section: Discussionmentioning

confidence: 99%

Radiolabeled Humanized Anti-CD3 Monoclonal Antibody Visilizumab for Imaging Human T-Lymphocytes

Malviya¹,

D’Alessandria²,

Bonanno³

et al. 2009

J Nucl Med

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Visilizumab is an IgG 2 humanized monoclonal antibody (mAb) characterized by non-FcgR binding and specific to the CD3 antigen, expressed on more than 95% of circulating resting T-lymphocytes and on activated T-lymphocytes homing in inflamed tissues. We hypothesized that the use of a radiolabeled anti-CD3 antibody might serve as a diagnostic tool for imaging T-cell traffic and lymphocytic infiltration of tissues and organs affected by autoimmune diseases. Here we describe the results of in vitro and animal experiments with 99m Tc-succinimidyl-6-hydrazinonicotinate hydrochloride (SHNH)-visilizumab. Methods: For mAb labeling, we used a 2-step method with a heterobifunctional linker SHNH. Several titrations were performed to obtain the best labeling efficiency. In vitro quality controls included stability assay, cysteine challenge, sodium dodecyl sulfate polyacrylamide gel electrophoresis, binding assay, and immunoreactivity assay. In vivo studies by high-resolution images were performed at 6 and 24 h after the injection of 99m Tc-SHNH-visilizumab. These included cell-targeting experiments in BALB/c mice xenografted subcutaneously with an increasing number of HuT78 cells in the leg and displaced with an excess of cold antibody. We also studied irradiated severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood mononuclear cells (hPBMCs) and injected with 99m Tclabeled visilizumab or control mAb. After dynamic imaging for 3 h, major organs were removed, counted, and processed for immunohistologic examination. Results: Visilizumab was labeled with HYNIC with high labeling efficiency (.90%) and high specific activity (SA; 10,360-11,100 MBq/mg), with retained biochemical integrity and in vitro binding activity to CD3-positive cells. The in vivo targeting experiment showed a proportional increase of specific uptake with the number of injected cells, both at 6 and at 24 h, and the in vivo competition study demonstrated more than 60% decreased uptake after an excess of unlabeled antibody. In SCID mice, hPBMCs in different tissues were detected by 99m Tc-labeled visilizumab and confirmed by histology. Conclusion: Visilizumab can be efficiently labeled with 99m Tc with high efficiency and SA and could be a valuable tool for the study of human T-lymphocyte trafficking and lymphocytic infiltration of tissues and organs.

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“…According to that, 89 Zr-labeled antibodies used in tumor detection at preclinic and clinic, successively [7,8,9]. On the other hand 89 Zrlabeled antibodies with cancer detection and research, there is also a potential for usage in autoimmune diseases [5,15]. There are also more studies about labeled of white-blood cells, cytokines and labeling of these cells are also important [11,14,19].…”

Section: Introductionmentioning

confidence: 99%

Analyzing of Production Conditions of 89Zr in the Particle Accelerator

Bulduk

Ünak

Kılçar

et al. 2019

Cumhuriyet Science Journal

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Nowadays 89Zr is outstanding PET radionuclide with its physical half-life (t1/2 ~ 78 hours), useful decay specifications and so that it is suitable for antibody-based immuno-PET. Relatively oscillated positrons' low decay energies supply to take high-resolution. 89Zr-labeled radiopharmaceuticals, especially as 89Zrlabeled antibodies applications are getting increase day by day.In this study, calculations about production of 89Zr were done and used (p,n) reaction of 89Y target system. For this Q-value, Threshold Energy, Minimum Coulomb Barrier Energy of the reaction were calculated then the cross-sections of this reaction were found using Empire3.2/MALTA code. After determining the irradiation calculations, the bombardment performed. The irradiation was performed in Ankara Sarayköy Nuclear Research and Training Center, proton accelerator. The cyclotron is IBA type Cyclone-30. Then separation part was done with Dowex resine system. After separation 89Zr from the irradiated target system, radioactive 89Zr was obtained purely..

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Radiopharmaceuticals for imaging chronic lymphocytic inflammation

Cited by 8 publications

References 66 publications

Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

Radiolabeled Humanized Anti-CD3 Monoclonal Antibody Visilizumab for Imaging Human T-Lymphocytes

Analyzing of Production Conditions of 89Zr in the Particle Accelerator

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