Research article summary (published 29 Sep 2009):

Intravesical alpha-radioimmunotherapy with 213Bi-anti-EGFR-mAb defeats human bladder carcinoma in xenografted nude mice.

Full Abstract

Transurethral resection of urothelial carcinoma often results in tumor recurrence due to disseminated tumor cells. Therefore, new therapeutic strategies are urgently needed. The aim of this study was to establish an orthotopic human bladder carcinoma mouse model using the epidermal growth factor receptor (EGFR)-overexpressing bladder carcinoma cell line EJ28 and to compare therapeutic efficacy of intravesically instilled alpha-particle-emitting (213)Bi-anti-EGFR-monoclonal antibody (mAb) with mitomycin C. METHODS: Female Swiss nu/nu mice were intravesically inoculated with luciferase-transfected EJ28 human bladder carcinoma cells after the induction of urothelial lesions by electrocautery. At different time points after cell inoculation, mice were treated intravesically with (213)Bi-anti-EGFR-mAb, mitomycin C, or unlabeled anti-EGFR-mAb. Tumor development and therapeutic response were evaluated via bioluminescence imaging. RESULTS: Mice without therapy and those treated with unlabeled anti-EGFR-mAb reached a median survival of 41 d and 89 d, respectively. Mice that underwent therapy with 0.925 MBq of (213)Bi-anti-EGFR-mAb 1 h, 7 d, or 14 d after cell instillation survived more than 300 d in 90%, 80%, and 40% of the cases, respectively. Therapy with 0.37 MBq 1 h or 7 d after tumor cell inoculation resulted in survival of more than 300 d in 90% and 50% of mice, respectively. Mitomycin C treatment after 1 h and 7 d prolonged survival to more than 300 d in 40% and 50%, respectively; however, treatment turned out to be nephrotoxic. In contrast, no signs of nephrotoxicity could be observed after (213)Bi-anti-EGFR-mAb treatment. CONCLUSION: The study suggests that radioimmunotherapy using intravesically instilled (213)Bi-anti-EGFR-mAb is a promising option for treatment of bladder cancer in patients.

Author information

Author/s: Pfost, Birgit (B); Seidl, Christof (C); Autenrieth, Michael (M); Saur, Dieter (D); Bruchertseifer, Frank (F); Morgenstern, Alfred (A); Schwaiger, Markus (M); Senekowitsch-Schmidtke, Reingard (R);

Affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med), published in United States. (Language: eng)

Reference: 2009-Oct; vol 50 (issue 10) : pp 1700-8

Dates: Created 2009/10/01; Completed 2009/11/03;

PMID: 19793735, status: MEDLINE (last retrieval date: 11/3/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Administration, Intravesical Alpha Particles - therapeutic use Animals Antibodies, Monoclonal - administration & dosage; immunology; pharmacokinetics; therapeutic use Bismuth - chemistry Cell Line, Tumor Female Humans Immunohistochemistry Luciferases, Firefly - genetics Luminescent Measurements Mice

Mice Mice, Nude Mitomycin - therapeutic use Radioimmunotherapy Radioisotopes Receptor, Epidermal Growth Factor - immunology Time Factors Tissue Distribution Transfection Treatment Outcome Urinary Bladder Neoplasms - drug therapy; metabolism; radiotherapy Xenograft Model Antitumor Assays

Associated Chemicals: Antibodies, Monoclonal (0) ; Radioisotopes (0) ; Mitomycin (50-07-7) ; Bismuth (7440-69-9) ; Luciferases, Firefly (EC 1.13.12.7) ; Receptor, Epidermal Growth Factor (EC 2.7.1.112)

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