European Journal of Nuclear Medicine and Molecular Imaging, 2018, Vol.45(8), pp.1364-1371
To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00259-018-4003-6 Byline: Michael E. Autenrieth (1), Christof Seidl (2,3), Frank Bruchertseifer (4), Thomas Horn (1), Florian Kurtz (1), Benedikt Feuerecker (3), Calogero D'Alessandria (3), Christian Pfob (3), Stephan Nekolla (3), Christos Apostolidis (4), Saed Mirzadeh (5), Jurgen E. Gschwend (1), Markus Schwaiger (3), Klemens Scheidhauer (3), Alfred Morgenstern (4) Keywords: Alpha-emitter 213.sup.Bi; 225.sup.Ac/ [.sup.213]Bi generator; Targeted therapy; Bladder cancer; Feasibility; Adverse effects; Therapeutic efficacy Abstract: Purpose Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Guerin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure. Methods A pilot study was conducted in 12 patients (age range 64--86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter 213.sup.Bi coupled to an anti-EGFR antibody (366--821 MBq). The primary aims of the study were to determine the feasibility of treatment with the 213.sup.Bi-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter. Results The study proved that intravesical instillation of the 213.sup.Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment. Conclusion Intravesical instillation of 213.sup.Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the 213.sup.Bi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned. Author Affiliation: (1) 0000000123222966, grid.6936.a, Department of Urology, Technische Universitat Munchen, Munich, Germany (2) 0000000123222966, grid.6936.a, Department of Obstetrics and Gynecology, Technische Universitat Munchen, Ismaninger Strasse 22, 81675, Munich, Germany (3) 0000000123222966, grid.6936.a, Department of Nuclear Medicine, Technische Universitat Munchen, Munich, Germany (4) grid.443865.8, European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany (5) 0000 0004 0446 2659, grid.135519.a, Nuclear Security and Isotope Technology Division, Oak Ridge National Laboratory, Oak Ridge, TN, 38731-6229, USA Article History: Registration Date: 23/03/2018 Received Date: 01/12/2017 Accepted Date: 23/03/2018 Online Date: 11/04/2018 Article note: Michael E. Autenrieth, Christof Seidl, Frank Bruchertseifer, Klemens Scheidhauer and Alfred Morgenstern contributed equally to this work.
Alpha-emitter Bi ; Ac/Bi generator ; Targeted therapy ; Bladder cancer ; Feasibility ; Adverse effects ; Therapeutic efficacy
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