186Re-labeled Monoclonal Antibody E48 Immunoglobulin G-mediated Therapy of Human Head and Neck Squamous Cell Carcinoma Xenografts

Martijn Gerretsen, Marijke van Walsum, Gordon B. Snow, Guus A.M.S. van Dongen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

In our laboratory, a solid-phase synthesis of 186Re-mercaptoacetyltriglycine for reproducible and aseptic production of stable I86Re-mono-clonal antibody conjugates was recently developed. Monoclonal antibody (MAb) E48 IgG, when labeled with 99mTc according to the same labeling procedure, was recently shown to be highly capable of detecting recurrent and metastatic disease in patients with head and neck squamous cell carcinoma. In the present study, MAb E48 was labeled with 186Re and tested for its capacity to eradicate established human head and neck squamous cell carcinoma xenografts growing s.c. in nude mice. Experimental groups received a single bolus injection of 200 [number of mice (n) = 6, number of tumors (t) = 11], 400 (n = 6, t = 11), 500 (n = 6, t = 12), or 600 (n = 5, t = 9) Ci 186Re-labeled MAb E48 IgG; control animals were given diluent (n = 4, t = 8). In the 200 Ci group, 5 of 11 tumors showed regression while the remaining tumors showed a decreased growth rate. In the other treatment groups, all tumors regressed. In all treatment groups, remissions were observed (no regrowth within 4 months after injection). The number of remissions in the 200, 400, 500, and 600 Ci group were 2 of 11 (18.2%), 3 of 11 (273%), 6 of 12 (50%), and 3 of 9 tumors (333%), respectively. In comparison with the median tumor volume doubling time of the controls, the tumor volume doubling time in the remaining tumors in the groups receiving 200,400,500, or 600 Ci was increased 5.5-, 7.8-, 8.7-, and 113-fold, respectively. Dosimetry was based on the biodistribution of 200 Ci 186Re-labeled MAb E48 IgG. In the group receiving 600 Ci, the absorbed cumulative radiation dose was 3432 cGy for tumor and 1356 cGy for blood. In other tissues, the accumulated dose was =17% of the dose delivered to tumor. The whole-body dose was 11-fold lower than the dose delivered to tumor. Apparent toxicity was limited to weight loss, which did not exceed 12% and which returned to control levels within 2 weeks. No treatment-related deaths occurred. These data suggest radioimmunotherapy with 186Re-labeled MAb E48 IgG to be a feasible approach for the treatment of head and neck cancer.

Original languageEnglish
Pages (from-to)3524-3529
Number of pages6
JournalCancer Research
Volume53
Issue number15
Publication statusPublished - 1 Jan 1993

Cite this

@article{9226c32b31724e6a9ba35d056cc3f6f9,
title = "186Re-labeled Monoclonal Antibody E48 Immunoglobulin G-mediated Therapy of Human Head and Neck Squamous Cell Carcinoma Xenografts",
abstract = "In our laboratory, a solid-phase synthesis of 186Re-mercaptoacetyltriglycine for reproducible and aseptic production of stable I86Re-mono-clonal antibody conjugates was recently developed. Monoclonal antibody (MAb) E48 IgG, when labeled with 99mTc according to the same labeling procedure, was recently shown to be highly capable of detecting recurrent and metastatic disease in patients with head and neck squamous cell carcinoma. In the present study, MAb E48 was labeled with 186Re and tested for its capacity to eradicate established human head and neck squamous cell carcinoma xenografts growing s.c. in nude mice. Experimental groups received a single bolus injection of 200 [number of mice (n) = 6, number of tumors (t) = 11], 400 (n = 6, t = 11), 500 (n = 6, t = 12), or 600 (n = 5, t = 9) Ci 186Re-labeled MAb E48 IgG; control animals were given diluent (n = 4, t = 8). In the 200 Ci group, 5 of 11 tumors showed regression while the remaining tumors showed a decreased growth rate. In the other treatment groups, all tumors regressed. In all treatment groups, remissions were observed (no regrowth within 4 months after injection). The number of remissions in the 200, 400, 500, and 600 Ci group were 2 of 11 (18.2{\%}), 3 of 11 (273{\%}), 6 of 12 (50{\%}), and 3 of 9 tumors (333{\%}), respectively. In comparison with the median tumor volume doubling time of the controls, the tumor volume doubling time in the remaining tumors in the groups receiving 200,400,500, or 600 Ci was increased 5.5-, 7.8-, 8.7-, and 113-fold, respectively. Dosimetry was based on the biodistribution of 200 Ci 186Re-labeled MAb E48 IgG. In the group receiving 600 Ci, the absorbed cumulative radiation dose was 3432 cGy for tumor and 1356 cGy for blood. In other tissues, the accumulated dose was =17{\%} of the dose delivered to tumor. The whole-body dose was 11-fold lower than the dose delivered to tumor. Apparent toxicity was limited to weight loss, which did not exceed 12{\%} and which returned to control levels within 2 weeks. No treatment-related deaths occurred. These data suggest radioimmunotherapy with 186Re-labeled MAb E48 IgG to be a feasible approach for the treatment of head and neck cancer.",
author = "Martijn Gerretsen and Walsum, {Marijke van} and Snow, {Gordon B.} and {van Dongen}, {Guus A.M.S.}",
year = "1993",
month = "1",
day = "1",
language = "English",
volume = "53",
pages = "3524--3529",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "15",

}

186Re-labeled Monoclonal Antibody E48 Immunoglobulin G-mediated Therapy of Human Head and Neck Squamous Cell Carcinoma Xenografts. / Gerretsen, Martijn; Walsum, Marijke van; Snow, Gordon B.; van Dongen, Guus A.M.S.

In: Cancer Research, Vol. 53, No. 15, 01.01.1993, p. 3524-3529.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - 186Re-labeled Monoclonal Antibody E48 Immunoglobulin G-mediated Therapy of Human Head and Neck Squamous Cell Carcinoma Xenografts

AU - Gerretsen, Martijn

AU - Walsum, Marijke van

AU - Snow, Gordon B.

AU - van Dongen, Guus A.M.S.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - In our laboratory, a solid-phase synthesis of 186Re-mercaptoacetyltriglycine for reproducible and aseptic production of stable I86Re-mono-clonal antibody conjugates was recently developed. Monoclonal antibody (MAb) E48 IgG, when labeled with 99mTc according to the same labeling procedure, was recently shown to be highly capable of detecting recurrent and metastatic disease in patients with head and neck squamous cell carcinoma. In the present study, MAb E48 was labeled with 186Re and tested for its capacity to eradicate established human head and neck squamous cell carcinoma xenografts growing s.c. in nude mice. Experimental groups received a single bolus injection of 200 [number of mice (n) = 6, number of tumors (t) = 11], 400 (n = 6, t = 11), 500 (n = 6, t = 12), or 600 (n = 5, t = 9) Ci 186Re-labeled MAb E48 IgG; control animals were given diluent (n = 4, t = 8). In the 200 Ci group, 5 of 11 tumors showed regression while the remaining tumors showed a decreased growth rate. In the other treatment groups, all tumors regressed. In all treatment groups, remissions were observed (no regrowth within 4 months after injection). The number of remissions in the 200, 400, 500, and 600 Ci group were 2 of 11 (18.2%), 3 of 11 (273%), 6 of 12 (50%), and 3 of 9 tumors (333%), respectively. In comparison with the median tumor volume doubling time of the controls, the tumor volume doubling time in the remaining tumors in the groups receiving 200,400,500, or 600 Ci was increased 5.5-, 7.8-, 8.7-, and 113-fold, respectively. Dosimetry was based on the biodistribution of 200 Ci 186Re-labeled MAb E48 IgG. In the group receiving 600 Ci, the absorbed cumulative radiation dose was 3432 cGy for tumor and 1356 cGy for blood. In other tissues, the accumulated dose was =17% of the dose delivered to tumor. The whole-body dose was 11-fold lower than the dose delivered to tumor. Apparent toxicity was limited to weight loss, which did not exceed 12% and which returned to control levels within 2 weeks. No treatment-related deaths occurred. These data suggest radioimmunotherapy with 186Re-labeled MAb E48 IgG to be a feasible approach for the treatment of head and neck cancer.

AB - In our laboratory, a solid-phase synthesis of 186Re-mercaptoacetyltriglycine for reproducible and aseptic production of stable I86Re-mono-clonal antibody conjugates was recently developed. Monoclonal antibody (MAb) E48 IgG, when labeled with 99mTc according to the same labeling procedure, was recently shown to be highly capable of detecting recurrent and metastatic disease in patients with head and neck squamous cell carcinoma. In the present study, MAb E48 was labeled with 186Re and tested for its capacity to eradicate established human head and neck squamous cell carcinoma xenografts growing s.c. in nude mice. Experimental groups received a single bolus injection of 200 [number of mice (n) = 6, number of tumors (t) = 11], 400 (n = 6, t = 11), 500 (n = 6, t = 12), or 600 (n = 5, t = 9) Ci 186Re-labeled MAb E48 IgG; control animals were given diluent (n = 4, t = 8). In the 200 Ci group, 5 of 11 tumors showed regression while the remaining tumors showed a decreased growth rate. In the other treatment groups, all tumors regressed. In all treatment groups, remissions were observed (no regrowth within 4 months after injection). The number of remissions in the 200, 400, 500, and 600 Ci group were 2 of 11 (18.2%), 3 of 11 (273%), 6 of 12 (50%), and 3 of 9 tumors (333%), respectively. In comparison with the median tumor volume doubling time of the controls, the tumor volume doubling time in the remaining tumors in the groups receiving 200,400,500, or 600 Ci was increased 5.5-, 7.8-, 8.7-, and 113-fold, respectively. Dosimetry was based on the biodistribution of 200 Ci 186Re-labeled MAb E48 IgG. In the group receiving 600 Ci, the absorbed cumulative radiation dose was 3432 cGy for tumor and 1356 cGy for blood. In other tissues, the accumulated dose was =17% of the dose delivered to tumor. The whole-body dose was 11-fold lower than the dose delivered to tumor. Apparent toxicity was limited to weight loss, which did not exceed 12% and which returned to control levels within 2 weeks. No treatment-related deaths occurred. These data suggest radioimmunotherapy with 186Re-labeled MAb E48 IgG to be a feasible approach for the treatment of head and neck cancer.

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M3 - Article

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JO - Cancer Research

JF - Cancer Research

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