ORIGINAL ARTICLES  ADVANCES IN RADIOIMMUNOIMAGING AND RADIOIMMUNOTHERAPY 

The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2007 December;51(4):334-42

Copyright © 2007 EDIZIONI MINERVA MEDICA

lingua: Inglese

Use of a 99mTc labeled anti-TNFα monoclonal antibody in Crohn’s disease: in vitro and in vivo studies

D’Alessandria C. ¹, Malviya G. ², Viscido A. ³, Aratari A. ³, Maccioni F. ⁴, Amato A. ⁵, Scopinaro F. ¹, Caprilli R. ³, Signore A. ^{1, 2}

¹ Nuclear Medicine Unit, II Faculty of Medicine La Sapienza University of Rome, Rome, Italy 2 Department of Nuclear Medicine and Molecular Imaging University Medical Center Groningen University of Groningen, Groningen, The Netherlands 3 Gastroenterology Unit, Department of Clinical Sciences La Sapienza University of Rome, Rome, Italy 4 Department of Radiological Sciences La Sapienza University of Rome, Rome, Italy 5 Department of Surgery, II Faculty of Medicine La Sapienza University of Rome, Rome, Italy

Aim. Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by a cellular-mediated immune response driven by cytokines secreted mainly by T helper 1 cells (Th1). In active phases of the disease, an increased production and release of tumor necrosis factor α (TNFα) by macrophages and monocytes of the lamina propria has been described. The aim of this study was to detect the presence of TNFα within the gut mucosa in patients with active CD by using 99mTc-labelled chimeric human/mouse monoclonal antibody anti-TNFα (Infliximab, Remicade®).
Methods. Infliximab has been labeled with 99mTc after reduction of disulfide bound by 2-ME method. In vitro binding assay and biodistribution in animal of [99mTc]Infliximab has been performed to evaluate the retention of its biological activity. Ten patients with active CD refractory to conventional medical therapies were studied. Images of the abdomen were acquired at 6 to 20 h after i.v. injection of about 10 mCi of [99mTc]Infliximab and a week later, all patients were also studied with [99mTc]HMPAO-labeled autologous white blood cells (WBC).
Results. A product with high labeling efficiency (>95%) and stability has been obtained. In vitro tests with stimulated T-cells expressing TNFα indicated that [99mTc] Infliximab retains its binding activity to cell bound TNFa as compared to unlabelled Infliximab. The degree of [99mTc]Infliximab uptake by the inflamed bowel evaluated at 20 h postinjection was much less than that seen with labeled WBC and with a different distribution. Three of these patients received anti-TNFα (Infliximab) for therapeutic purposes with good clinical results despite the scintigraphy with 99mTc-Infliximab was negative in 2 of them.
Conclusion. Scintigraphy with [99mTc]Infliximab shows the presence of little TNFα in the affected bowel of patients with active CD. Therefore, the clinical benefit that patients have from Infliximab therapy is unlikely the consequence of a local a reduction of TNFα and the mechanism of action of Infliximab, in therapeutic doses, deserves further investigations.