Malviya, G. , Dierckx, R.A. and Signore, A. (2009) Radiolabeling of a Fully Human Anti-DR Monoclonal Antibody with 99m-technetium: A Potential New Imaging Agent for Lymphoma and Autoimmunity. Annual Congress of the European Association of Nuclear Medicine 2009, Barcelona, Spain, 10-14 Oct 2009. S404.
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Abstract
1D09C3 is a fully humanised IgG4 monoclonal antibody (mAb), due to this it does not have Fc‐ portion‐mediated side effects, which may present in chimeric antibodies. It is known that HLA‐DR protein status predicts survival in patients with B‐cell lymphomas, but it is not yet known whether it is possible to obtain this information in‐vivo by non‐invasive imaging modalities. Furthermore, HLA‐DR antigens are over expressed in situ in a variety of autoimmune diseases, including Rheumatoid Arthritis. Aim: The rationale of the present study was to radiolabel 1D09C3 with 99m‐technetium for the in‐vivo histological characterisation of HLA‐DR +ve cells in lymphoma patients and patients with RA. Materials and methods: For radiolabeling we compared a direct method via 2‐ME reduction of disulphide bonds with a two‐step method using a hetero‐bifunctional linker SHNH/S‐HYNIC (succinimidyl‐6‐hydrazinonicotinate hydrochloride). Binding assay was performed on DR +ve cell line. Several titrations were performed to obtain best labeling efficiency (LE) and specific activity (SA). In‐vitro quality controls included stability assay in plasma, SDS‐PAGE, autoradiography, Cysteine challenge and immunoreactive fraction assay. Results: Anti‐DR mAb (1D09C3) was best labeled with a direct method via 2‐ME reduction with a high labeling efficiency (LE >95%) and high specific activity (SA = 150 mCi/mg) with retained biochemical integrity and binding activity. SDS‐PAGE and autoradiography analysis demonstrated its structural integrity, moreover, Cysteine challenge and immunorective fraction assay also confirms its in‐vitro stability and binding specificity to the HLA‐DR +ve cells. Conclusion: 1D09C3 can be efficiently labeled with 99mTc with high LE and SA, using a direct labeling method with 2‐ME reduction. Radiolabeled 1D09C3 binds to human HLA‐DR antigens, therefore, can be used as a prognostic/diagnostic tool in lymphoma patients or in several autoimmune diseases. In vivo studies are in progress.
| Item Type: | Conference or Workshop Item |
|---|---|
| Additional Information: | Abstract of poster presentation - available in European Journal of Nuclear Medicine and Molecular Imaging 36(2_suppl): S404 |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Malviya, Dr Gaurav |
| Authors: | Malviya, G., Dierckx, R.A., and Signore, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | European Journal of Nuclear Medicine and Molecular Imaging |
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