Targeting Superficial Bladder Cancer by the Intravesical Administration of Copper-67–Labeled Anti-MUC1 Mucin Monoclonal Antibody C595

Hughes, O. D. M.; Bishop, M. C.; Perkins, Alan C.; Wastie, M. L.; Denton, G.; Price, Michael R.; Frier, M.; Denley, Helen; Rutherford, Richard A.D.; Schubiger, P. August

doi:10.1200/jco.2000.18.2.363

Cited by 62 publications

(37 citation statements)

References 19 publications

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“…MUC1 may provide a good basis for targeting pancreatic cancer cells in transit or in preangiogenic cancer cell clusters. MAb C595 has been labelled with 67 Cu and 188 Re for radioimmunotherapy in bladder cancer (Hughes et al, 1997(Hughes et al, , 2000aMurray et al, 2001).…”

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confidence: 99%

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

et al. 2004

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Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using 213 Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of 213 Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in B90% of tested tumour samples and the three pancreatic cancer cell lines. 213 Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel 213 Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. 213 Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen.

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confidence: 99%

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

et al. 2004

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“…Tumor uptake of 67 Cu-anti-C595-mAb targeting MUC1 could be demonstrated preclinically (34). In a first clinical study, intravesical instillation of 67 Cu-anti-C595-mAb successfully targeted superficial bladder cancer in 12 of 15 patients (35). However, we observed a low binding of 213 Bi-anti-MUC1-mAb to EJ28-luc-bladder carcinoma cells, suggesting weak expression of MUC1.…”

Section: Discussionmentioning

confidence: 85%

Intravesical α-Radioimmunotherapy with ²¹³Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice

Pfost¹,

Seidl

Autenrieth

et al. 2009

J Nucl Med

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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 a-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.

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“…Monoclonal antibodies have been radiolabelled with 111 In and 99m Tc (8,9,39-42) for SPECT and scintigraphy imaging. Both 67 Cu and 188 Re have been suggested (11)(12)(13) as nuclides to be used for the therapy of bladder cancer. However, reported cystological data obtained from patients treated through direct instillation with targeting immunoagents generally indicate low uptake of radioactivity.…”

Section: Discussionmentioning

confidence: 99%

“…New radioimmunotherapeutical conjugates have been developed in the last 15 years with the prospect of treating bladder cancer through such procedures. Most of these involved antibodies radiolabelled with 111 In (8,9), 131 I (10), 67 Cu (11,12), 188 Re (13). However, the large size of monoclonal antibodies (~150 kD) is a general limitation to the efficiency of intravesical treatments due to slow diffusion and limited penetration.…”

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confidence: 99%

Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma

Fortin

Orlova²,

Malmström³

et al. 2007

Int J Mol Med

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Abstract. The direct instillation of radiolabelled conjugates in the urinary bladder is a promising path for the treatment of bladder carcinoma. The targeting of HER2/neu receptors expressed on the surface of many bladder carcinoma cells shows potential to be developed as a therapeutic strategy, and patients identified with a high risk of progression may benefit from adjuvant targeted radionuclide therapy. A phage-display selected Affibody molecule (Z HER2:342 ) which binds to HER2/ neu with picomolar affinity, can be used for targeting HER2/ neu-expressing bladder carcinomas. A DOTA-derivative of Z HER2:342 , designated as DOTA-Z HER2:342 -3, is considered as a suitable targeting agent for therapy. The DOTA chelator provides stable labelling with radiometals, and the low molecular weight (7.2 kDa) of the DOTA-Z HER2:342 -3 compound is expected to enable efficient tumor penetration. DOTA-Z HER2:342 -3 was radiolabelled with 90 Y and 177 Lu in 1 M ammonium acetate buffer, at pH 5.5, and in the presence of ascorbic acid. Nearly quantitative labelling yields were achieved for both nuclides after 15 min of incubation at 60˚C. After chelation, the conjugates retained their capacity to specifically bind to HER2/neu-expressing SKOV-3 cells. The radiolabelled affibody conjugate (DOTA-Z HER2:342 -3) demonstrated high antigen-binding capacity and good cellular retention. Biodistribution in normal mice demonstrated low uptake in all organs and tissues except for kidneys.

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Targeting Superficial Bladder Cancer by the Intravesical Administration of Copper-67–Labeled Anti-MUC1 Mucin Monoclonal Antibody C595

Abstract: This study indicates a promising method for the treatment of superficial bladder cancer. Although the mean initial tumor uptake was high, effective therapy of bladder tumors will require an increased retention of the cytotoxic radionuclide in tumor tissue.

Cited by 62 publications

References 19 publications

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

Intravesical α-Radioimmunotherapy with ²¹³Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice

Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma

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Targeting Superficial Bladder Cancer by the Intravesical Administration of Copper-67–Labeled Anti-MUC1 Mucin Monoclonal Antibody C595

Abstract: This study indicates a promising method for the treatment of superficial bladder cancer. Although the mean initial tumor uptake was high, effective therapy of bladder tumors will require an increased retention of the cytotoxic radionuclide in tumor tissue.

Cited by 62 publications

References 19 publications

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213Bi-C595 radioimmunoconjugate

Intravesical α-Radioimmunotherapy with 213Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice

Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma

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Product

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Intravesical α-Radioimmunotherapy with ²¹³Bi-Anti-EGFR-mAb Defeats Human Bladder Carcinoma in Xenografted Nude Mice