Efficacy and toxicity of radioimmunotherapy with 90Y-DOTA-peptide-ChL6 for PC3-tumored mice

Robert T O'Donnell, Sally J. DeNardo, Gerald L Denardo, Laird Miers, Kathleen R. Lamborn, David L. Kukis, Frederick J Meyers

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

BACKGROUND. Radioimmunotherapy (RIT) is a new therapeutic modality capable of systemic delivery of radionuclides specifically to sites of metastatic cancer. The L6 monoclonal antibody has been shown to target prostate cancer in preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in breast cancer patients. METHODS. Pharmacokinetics, blood counts, body weight, and antitumor activity of RIT with 90yttrium- (90Y)-DOTA-peptide-ChL6 (75-260 μCi) were determined in nude mice bearing human prostate cancer (PC3) xenografts. RESULTS. RIT produced durable, dose- dependent antitumor effects with a 100% response rate using 112 μCi and 150 μCi (the maximum tolerated dose) of 90y-DOTA-peptide-ChL6. Myelotoxicity was reversible, dose-limiting, and dose-related. RIT was associated with improved survival (P = 0.05). All 5 mice in the 150-μCi group survived the 84-day study period vs. 1/8 (13%) for untreated, tumored control mice. CONCLUSIONS. 90y-DOTA-peptide-ChL6 targets PC3 human prostate cancer xenografts in nude mice and has an antitumor effect. These results provide a basis for future RIT trials for patients with metastatic prostate cancer. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)187-192
Number of pages6
JournalProstate
Volume44
Issue number3
DOIs
StatePublished - Aug 1 2000

Fingerprint

Radioimmunotherapy
Peptides
Prostatic Neoplasms
Heterografts
Nude Mice
Maximum Tolerated Dose
Radioisotopes
Pharmacokinetics
Monoclonal Antibodies
Body Weight
Breast Neoplasms
Survival
Neoplasms

Keywords

  • Chimeric L6
  • Nude mice
  • PC3
  • Prostate cancer
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Urology

Cite this

Efficacy and toxicity of radioimmunotherapy with 90Y-DOTA-peptide-ChL6 for PC3-tumored mice. / O'Donnell, Robert T; DeNardo, Sally J.; Denardo, Gerald L; Miers, Laird; Lamborn, Kathleen R.; Kukis, David L.; Meyers, Frederick J.

In: Prostate, Vol. 44, No. 3, 01.08.2000, p. 187-192.

Research output: Contribution to journalArticle

O'Donnell, Robert T ; DeNardo, Sally J. ; Denardo, Gerald L ; Miers, Laird ; Lamborn, Kathleen R. ; Kukis, David L. ; Meyers, Frederick J. / Efficacy and toxicity of radioimmunotherapy with 90Y-DOTA-peptide-ChL6 for PC3-tumored mice. In: Prostate. 2000 ; Vol. 44, No. 3. pp. 187-192.
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N2 - BACKGROUND. Radioimmunotherapy (RIT) is a new therapeutic modality capable of systemic delivery of radionuclides specifically to sites of metastatic cancer. The L6 monoclonal antibody has been shown to target prostate cancer in preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in breast cancer patients. METHODS. Pharmacokinetics, blood counts, body weight, and antitumor activity of RIT with 90yttrium- (90Y)-DOTA-peptide-ChL6 (75-260 μCi) were determined in nude mice bearing human prostate cancer (PC3) xenografts. RESULTS. RIT produced durable, dose- dependent antitumor effects with a 100% response rate using 112 μCi and 150 μCi (the maximum tolerated dose) of 90y-DOTA-peptide-ChL6. Myelotoxicity was reversible, dose-limiting, and dose-related. RIT was associated with improved survival (P = 0.05). All 5 mice in the 150-μCi group survived the 84-day study period vs. 1/8 (13%) for untreated, tumored control mice. CONCLUSIONS. 90y-DOTA-peptide-ChL6 targets PC3 human prostate cancer xenografts in nude mice and has an antitumor effect. These results provide a basis for future RIT trials for patients with metastatic prostate cancer. (C) 2000 Wiley-Liss, Inc.

AB - BACKGROUND. Radioimmunotherapy (RIT) is a new therapeutic modality capable of systemic delivery of radionuclides specifically to sites of metastatic cancer. The L6 monoclonal antibody has been shown to target prostate cancer in preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in breast cancer patients. METHODS. Pharmacokinetics, blood counts, body weight, and antitumor activity of RIT with 90yttrium- (90Y)-DOTA-peptide-ChL6 (75-260 μCi) were determined in nude mice bearing human prostate cancer (PC3) xenografts. RESULTS. RIT produced durable, dose- dependent antitumor effects with a 100% response rate using 112 μCi and 150 μCi (the maximum tolerated dose) of 90y-DOTA-peptide-ChL6. Myelotoxicity was reversible, dose-limiting, and dose-related. RIT was associated with improved survival (P = 0.05). All 5 mice in the 150-μCi group survived the 84-day study period vs. 1/8 (13%) for untreated, tumored control mice. CONCLUSIONS. 90y-DOTA-peptide-ChL6 targets PC3 human prostate cancer xenografts in nude mice and has an antitumor effect. These results provide a basis for future RIT trials for patients with metastatic prostate cancer. (C) 2000 Wiley-Liss, Inc.

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