Radioimmunotherapy of human colon carcinoma xenografts using a 213Bi-labeled domain-deleted humanized monoclonal antibody

Diane Milenic, Kayhan Garmestani, Ekaterina Dadachova, Lara Chappell, Paul Albert, Donald Hill, Jeffrey Schlom, Martin Brechbiel

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The data presented within this paper is the first report of a humanized domain-deleted monoclonal antibody (HuCC49ΔCH2) to be utilized in a radioimmunotherapeutic (RIT) application with 213Bi. An initial study indicated that 111In-HuCC49ΔCH2 targets the subcutaneously implanted human colon carcinoma xenograft, LS-174T, when injected via a peritoneal route. The HuCC49ΔCH2 was then radiolabeled with 213Bi, an α-emitting radionuclide with a half-life of 45. 6 minutes, and evaluated for therapeutic efficacy. Dose titration studies indicated that a single dose of 500-1000 μCi, when injected by an intraperitoneal route, resulted in the growth inhibition or regression of the tumor xenograft. The radioimmunotherapeutic effect was found to be dose-dependent. Specificity of the therapeutic efficacy was confirmed in a subsequent experiment with athymic mice bearing TAG-72 negative MIP (human colorectal) xenografts. A preliminary study was also performed to assess a multiple-dose administration of 213Bi-HuCC49ΔCH2. Doses (500 μCi) were administered at 14-day intervals after tumor implantation. A reduction in volume and/or delay in tumor growth was evident following the second and third injections of 213Bi-HuCC49ΔCH2. As further validation of the use of 213Bi-HUCC49ΔCH2 for RIT, a study using 131I was conducted. The overall survival of mice receiving 213Bi-HuCC49ΔCH2 was greater than those that received 131I-HUCC49ΔCH2.

Original languageEnglish (US)
Pages (from-to)135-147
Number of pages13
JournalCancer Biotherapy and Radiopharmaceuticals
Volume19
Issue number2
DOIs
StatePublished - 2004
Externally publishedYes

Fingerprint

Radioimmunotherapy
Antibodies, Monoclonal, Humanized
Heterografts
Colon
Carcinoma
Neoplasms
Growth
Nude Mice
Radioisotopes
Half-Life
Monoclonal Antibodies
Injections
Therapeutics

Keywords

  • α-particle
  • Bi
  • Bismuth
  • HuCC49ΔCH2
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Radioimmunotherapy of human colon carcinoma xenografts using a 213Bi-labeled domain-deleted humanized monoclonal antibody. / Milenic, Diane; Garmestani, Kayhan; Dadachova, Ekaterina; Chappell, Lara; Albert, Paul; Hill, Donald; Schlom, Jeffrey; Brechbiel, Martin.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 19, No. 2, 2004, p. 135-147.

Research output: Contribution to journalArticle

Milenic, D, Garmestani, K, Dadachova, E, Chappell, L, Albert, P, Hill, D, Schlom, J & Brechbiel, M 2004, 'Radioimmunotherapy of human colon carcinoma xenografts using a 213Bi-labeled domain-deleted humanized monoclonal antibody', Cancer Biotherapy and Radiopharmaceuticals, vol. 19, no. 2, pp. 135-147. https://doi.org/10.1089/108497804323071904
Milenic, Diane ; Garmestani, Kayhan ; Dadachova, Ekaterina ; Chappell, Lara ; Albert, Paul ; Hill, Donald ; Schlom, Jeffrey ; Brechbiel, Martin. / Radioimmunotherapy of human colon carcinoma xenografts using a 213Bi-labeled domain-deleted humanized monoclonal antibody. In: Cancer Biotherapy and Radiopharmaceuticals. 2004 ; Vol. 19, No. 2. pp. 135-147.
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AB - The data presented within this paper is the first report of a humanized domain-deleted monoclonal antibody (HuCC49ΔCH2) to be utilized in a radioimmunotherapeutic (RIT) application with 213Bi. An initial study indicated that 111In-HuCC49ΔCH2 targets the subcutaneously implanted human colon carcinoma xenograft, LS-174T, when injected via a peritoneal route. The HuCC49ΔCH2 was then radiolabeled with 213Bi, an α-emitting radionuclide with a half-life of 45. 6 minutes, and evaluated for therapeutic efficacy. Dose titration studies indicated that a single dose of 500-1000 μCi, when injected by an intraperitoneal route, resulted in the growth inhibition or regression of the tumor xenograft. The radioimmunotherapeutic effect was found to be dose-dependent. Specificity of the therapeutic efficacy was confirmed in a subsequent experiment with athymic mice bearing TAG-72 negative MIP (human colorectal) xenografts. A preliminary study was also performed to assess a multiple-dose administration of 213Bi-HuCC49ΔCH2. Doses (500 μCi) were administered at 14-day intervals after tumor implantation. A reduction in volume and/or delay in tumor growth was evident following the second and third injections of 213Bi-HuCC49ΔCH2. As further validation of the use of 213Bi-HUCC49ΔCH2 for RIT, a study using 131I was conducted. The overall survival of mice receiving 213Bi-HuCC49ΔCH2 was greater than those that received 131I-HUCC49ΔCH2.

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