PURPOSE: (131)I- and (90)Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (<20 min) with either (177)Lu or (90)Y. MATERIALS AND METHODS: Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. RESULTS: The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10(5) times excess of diethylenetriaminepentaacetic acid (DTPA, 37 degrees C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m(2) body surface (177)Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of (177)Lu-DOTA-rituximab was tolerated well. CONCLUSION: Our results show that DOTA-rituximab (4:1) can be labelled with (177)Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. (177)Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL.
PURPOSE: (131)I- and (90)Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (<20 min) with either (177)Lu or (90)Y. MATERIALS AND METHODS: Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. RESULTS: The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10(5) times excess of diethylenetriaminepentaacetic acid (DTPA, 37 degrees C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m(2) body surface (177)Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of (177)Lu-DOTA-rituximab was tolerated well. CONCLUSION: Our results show that DOTA-rituximab (4:1) can be labelled with (177)Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. (177)Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL.
Authors: G A Wiseman; C A White; T E Witzig; L I Gordon; C Emmanouilides; A Raubitschek; N Janakiraman; J Gutheil; R J Schilder; S Spies; D H Silverman; A J Grillo-López Journal: Clin Cancer Res Date: 1999-10 Impact factor: 12.531
Authors: Oliver W Press; Joseph M Unger; Rita M Braziel; David G Maloney; Thomas P Miller; Michael Leblanc; Richard I Fisher Journal: J Clin Oncol Date: 2006-08-08 Impact factor: 44.544
Authors: Gregory A Wiseman; Ellen Kornmehl; Bryan Leigh; William D Erwin; Donald A Podoloff; Stewart Spies; Richard B Sparks; Michael G Stabin; Thomas Witzig; Christine A White Journal: J Nucl Med Date: 2003-03 Impact factor: 10.057
Authors: Thomas E Witzig; Christine A White; Leo I Gordon; Gregory A Wiseman; Christos Emmanouilides; James L Murray; John Lister; Pratik S Multani Journal: J Clin Oncol Date: 2003-04-01 Impact factor: 44.544
Authors: M S Kaminski; J Estes; K R Zasadny; I R Francis; C W Ross; M Tuck; D Regan; S Fisher; J Gutierrez; S Kroll; R Stagg; G Tidmarsh; R L Wahl Journal: Blood Date: 2000-08-15 Impact factor: 22.113
Authors: Gregory A Wiseman; Bryan Leigh; William D Erwin; Dominick Lamonica; Ellen Kornmehl; Stewart M Spies; Daniel H S Silverman; Thomas E Witzig; Richard B Sparks; Christine A White Journal: Cancer Date: 2002-02-15 Impact factor: 6.860
Authors: Arutselvan Natarajan; Gayatri Gowrishankar; Carsten H Nielsen; Sen Wang; Andrei Iagaru; Michael L Goris; Sanjiv Sam Gambhir Journal: Mol Imaging Biol Date: 2012-10 Impact factor: 3.488
Authors: Erika Elgström; Sophie E Eriksson; Otto Ljungberg; Pär-Ola Bendahl; Tomas G Ohlsson; Rune Nilsson; Jan Tennvall Journal: EJNMMI Res Date: 2015-09-15 Impact factor: 3.138
Authors: Arne Kolstad; Tim Illidge; Nils Bolstad; Signe Spetalen; Ulf Madsbu; Caroline Stokke; Johan Blakkisrud; Ayca Løndalen; Noelle O'Rourke; Matthew Beasley; Wojciech Jurczak; Unn-Merete Fagerli; Michal Kaščák; Mike Bayne; Aleš Obr; Jostein Dahle; Lisa Rojkjaer; Veronique Pascal; Harald Holte Journal: Blood Adv Date: 2020-09-08
Authors: Dhanusha Sabanathan; Douglas H Campbell; Vicki M Velonas; Sandra Wissmueller; Hubert Mazure; Marko Trifunovic; Pirooz Poursoltan; Kevin Ho Shon; Tiffany R Mackay; Maria E Lund; Yanling Lu; Paul J Roach; Dale L Bailey; Bradley J Walsh; David Gillatt; Howard Gurney Journal: Asia Ocean J Nucl Med Biol Date: 2021