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The potential of radiolabeled EGF‐dextran conjugates in the treatment of urinary bladder carcinoma
Author(s) -
Bue Peter,
Márquez Marcela,
Malmström PerUno,
Westlin JanErik,
Nilsson Sten,
Holmberg Anders R.
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971215)80:12+<2385::aid-cncr8>3.0.co;2-a
Subject(s) - medicine , dextran , conjugate , urinary bladder , urology , carcinoma , urinary system , cancer research , oncology , biochemistry , biology , mathematical analysis , mathematics
BACKGROUND Muscle‐invasive urothelial carcinoma of the urinary bladder has a poor prognosis in spite of available therapies. These tumors frequently overexpress the epidermal growth factor receptor (EGFr), a possible target for therapeutic conjugates. The aim of this study was to construct an EGF‐carbohydrate conjugate that would be potentially useful for both local (i.e., intravesical) and systemic radiotherapy. METHODS EGF was coupled to periodate activated dextran by reductive amination. Receptor binding tests in vitro were conducted, using the human urothelial carcinoma cell line RT4 and the human malignant glioma cell line U‐343‐MG as a positive control. In the in vivo experiments, nude mice with subcutaneously grown xenografts of the RT4 tumor were injected intravenously with technetium‐99m‐labeled EGF conjugates. Samples of organs, blood, and tumors were collected after 24 hours. The radioactive uptake was calculated as a percentage of the dose per gram of tissue. RESULTS The specific binding in the in vitro experiment was 90‐95%. The binding was similar in both cell lines. There was a positive uptake in the tumors in the in vivo experiment, with tumor‐to‐blood ratios from 2:1 to 6:1. The uptake level in the kidneys was similar to that in the tumors (i.e., ∼0.05% dose per gram of tissue). The other organs had a lower uptake compared with the tumor uptake. CONCLUSIONS The results indicate that radiolabeled EGF‐dextran has the potential to become a tool for local treatment of recurrent bladder carcinoma. With appropriate modifications, it should be possible to use this conjugate for systemic radiotherapy as well. Cancer 1997; 80:2385‐9. © 1997 American Cancer Society.