http://www.cnr.it/ontology/cnr/individuo/prodotto/ID239503

Radiolabeled-Visilizumab, a humanized anti-CD3 monoclonal antibody, for in vivo targeting of human CD3+ lymphocytes (Comunicazione a convegno)

Type

Prodotto della ricerca (Classe)
Comunicazione a convegno (Classe)

Label

Radiolabeled-Visilizumab, a humanized anti-CD3 monoclonal antibody, for in vivo targeting of human CD3+ lymphocytes (Comunicazione a convegno) (literal)

Anno

2008-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1007/s00259-008-0904-0 (literal)

Alternative label

Malviya, G.;D'Alessandria, C.;Trotta, C.;Massari, R.;Soluri, A.;Scopinaro, F.;Dierckx, R. A.;Signore, A. (2008)
Radiolabeled-Visilizumab, a humanized anti-CD3 monoclonal antibody, for in vivo targeting of human CD3+ lymphocytes
in Congress EANM - European Association of Nuclear Medicine 2008, MUNICH (Germany), 11-15/10/2008
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Malviya, G.;D'Alessandria, C.;Trotta, C.;Massari, R.;Soluri, A.;Scopinaro, F.;Dierckx, R. A.;Signore, A. (literal)

Pagina inizio

S142 (literal)

Pagina fine

S142 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni

Presentazione orale (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://biblioproxy.cnr.it:2106/article/10.1007/s00259-008-0904-0 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#titoloVolume

European Journal of Nuclear Medicine and Molecular Imaging (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

35 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#volumeInCollana

35 (literal)

Rivista

European journal of nuclear medicine and molecular imaging (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

1 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

2 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

1, 7: Dept. Nuclear Medicine & Molecular Imaging, University Medical Center Groningen, Groningen,NETHERLANDS; 2, 6, 8: Nuclear Medicine, 2nd Faculty of Medicine, \"Sapienza\" University, Roma, ITALY; 3, 4, 5: Istituto di Ingegneria Biomedica (ISIB) - National Council of Research, Sezione di Roma, Roma, ITALY. (literal)

Titolo

Radiolabeled-Visilizumab, a humanized anti-CD3 monoclonal antibody, for in vivo targeting of human CD3+ lymphocytes (literal)

Abstract

Visilizumab is an IgG2 mAb binding to CD3 expressed on circulating human peripheral T cells and activated T cells in inflamed tissues. Visilizumab and other anti-CD3 mAbs have been proposed for treatment of various immune-mediated inflammatory diseases. Aims of present study were (1) to radiolabel visilizumab with technetium-99m and (2) to validate the binding activity of the radiolabelled visilizumab in athymic nude mice engrafted with CD3+ tumor cells or with human peripheral blood lymphocytes (hPBL). For labelling we compared a direct labelling method via 2ME 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 HuT 78 cell line. In-vivo studies included a tumour targeting experiment in 9 athymic nude Balb/c mice xenografted subcutaneously with increasing number of HuT 78 cells in the leg (5x106, 10x106 and 20x106). On the contra lateral thigh, animals were implanted with 10x106 CD3 negative tumor cells as control. Two hours after implant mice were injected in a tail vein with about 30 µCi (about 100 ng) of radiolabelled Visilizumab. High resolution portable gamma camera (5x5cm field of view; 2mm spatial resolution) images were acquired 6h and 24h after injection and target to background radioactivity ratios were calculated. The ability of radiolabelled antibody to study the human lymphocyte trafficking in different organs was tested in SCID mice model followed by 99mTc-visilizumab injection (or control antibody) and dynamic high resolution imaging up to 3h. Then, organs were collected in formalin vials and immunohistological examination was performed to count CD3+ cells in tissues to be compared with radioactivity counted in organs. Visilizumab was best labelled with HYNIC with a high labelling efficiency (LE>90%) and high specific activity (SA=280-320mCi/mg) with retained biochemical integrity and in vitro binding activity. In tumor targeting experiment, we observed an increase of uptake of radiolabelled mAb to CD3+ cells compared to CD3- cells and the binding activity was proportional to the number of injected cells, both at 6h and 24h. In SCID mice, hPBMCs in tissues were detected by 99mTc-labelled visilizumab and confirmed by histology. Thus, radiolabelled Visilizumab preferably binds to grafted human T cell in SCID mice and could be a valuable tool to examine biodistribution of visilizumab in subjects or for imaging T cell traffic and lymphocytic infiltration in tissues and organs. (literal)

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