title: A novel platform for radioimmunotherapy: extracorporeal depletion of biotinylated and 90Y-labeled rituximab in patients with refractory B-cell lymphoma.
abstract: 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)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 (111)In-rituximab-biotin for immunoscintigraphy. A week later, the patients were treated with another 250 mg/m(2) rituximab followed by (111)In/-(90)Y-rituximab-biotin (11 or 15 (90)Y MBq/kg). ECAT was performed 48 hours later. All 8 patients receiving (111)In-rituximab-biotin showed tumor uptake. Seven patients received radioimmunotherapy and subsequent ECAT. The mean depletion of (90)Y-rituximab-biotin in whole blood after ECAT 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.
authors.affiliation: Department of Oncology, Lund University Hospital, Lund, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Lindén
authors.forename: Jan
authors.initials: J
authors.lastname: Kurkus
authors.forename: Michael
authors.initials: M
authors.lastname: Garkavij
authors.forename: Eva
authors.initials: E
authors.lastname: Cavallin-Ståhl
authors.forename: Michael
authors.initials: M
authors.lastname: Ljungberg
authors.forename: Rune
authors.initials: R
authors.lastname: Nilsson
authors.forename: Tomas
authors.initials: T
authors.lastname: Ohlsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Sandberg
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Strand
authors.forename: Jan
authors.initials: J
authors.lastname: Tennvall
mesh_terms: D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001710:Biotin; D019921:Biotinylation; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D006382:Hemadsorption; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007205:Indium Radioisotopes / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000628:therapy*; D016719:Radioimmunodetection; D016499:Radioimmunotherapy / Q000379:methods*; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D000069283:Rituximab; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018796:Immunoconjugates; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D000069283:Rituximab; D001710:Biotin