A novel platform for radioimmunotherapy: Extracorporeal depletion of biotinylated and Y-90-labeled rituximab in patients with refractory B-cell lymphoma

作者：Linden O; Kurkus J; Garkavij M; Cavallin Stahl E; Ljungberg M; Nilsson R; Ohlsson T; Sandberg B; Strand SE; Tennvall J^*

来源：Cancer Biotherapy and Radiopharmaceuticals, 2005, 20(4): 457-466.

DOI：10.1089/cbr.2005.20.457

• lymphoma
• radioimmunotherapy
• rituximab
• (90)yttrium
• extracorporeal adsorption

Radioimmunotherapy is limited by the absorbed dose to radiosensitive organs. Removal of circulating radiolabeled MAbs after tumor tissue has been optimally targeted and should permit the administration of higher radioactivity to patients, resulting in a higher absorbed tumor dose. A novel "extracorporeal affinity adsorption treatment" (ECAT) device (MitraDep (c)) was tested, with which biotinylated and radiolabeled MAbs can be removed from the circulation by passing whole blood over a filter coated with avidin. The antibodies were simultaneously radiolabeled and biotinylated using a trifunctional moiety comprising DOTA and biotin. Eight patients-all but 1 of whom with aggressive or mantle cell B-cell lymphoma-who had failed to respond-to standard therapies received infusions of 250 mg/m(2) cold rituximab and 150 MBq In-111-rituximab-biotin for immunoscintigraphy. A week later, the patients were treated with another 250 mg/m2 rituximab followed by In-111/-Y-90-rituximab-biotin (11 or 15 Y-90 MBq/kg). ECAT was performed 48 hours later. All 8 patients receiving In-111-rituximab-biotin showed tumor uptake. Seven patients received radioimmunotherapy and subsequent ECAT. The mean depletion of Y-90-rituximab-biotin in whole blood after SCAT was 96%, in the whole body 49%, in the lungs 62%, and in the liver and kidneys 40%. No effects on patients' vital signs and no adverse effects on hematological or coagulation parameters was observed during the ECAT procedure. A dose-escalation study is initiated.

• 出版日期2005-8