Radioimmunotherapy for breast cancer using indium- 111/Yttrium-90 BrE- 3: Results of a phase I clinical trial

S. J. DeNardo, E. L. Kramer, Robert T O'Donnell, Carol M Richman, Q. A. Salako, S. Shen, M. Noz, S. D. Glenn, R. L. Ceriani, Gerald L Denardo

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

BrE-3 is a murine IgG1 monoclonal antibody that binds to 97% of human ductal breast cancer specimens. A previous study documented the ability of 111In-labeled 1,4-methyl-benzyl isothiocyanate diethylenetriamine pentaacetic acid (111In-MX-DTPA) BrE-3 to specifically target breast cancer tissue in patients, and the dosimetry derived from the pharmacokinetics suggested that a useful therapeutic index could be obtained with 90Y-MX-DTPA BrE-3. A Phase I maximum tolerated dose study was, therefore, initiated. Methods: Six patients received 111In/90Y-MX-DTPA BrE-3, three of them receiving 6.25 and the other three receiving 9.25 mCi/m2 of 90Y. Pharmacokinetics, dosimetry, human anti-mouse antibody (HAMA), toxicity and clinical responses were evaluated. Results: Three of six patients demonstrated a minor and transient, but objective tumor response, and none of the patients had significant toxicity. Tumor dosimetry ranged from 39 to 167 rad/mCi of 90Y (442-1887 rad/dose). HAMA response occurred in five of six patients. Conclusion: Minimal toxicity, dosimetric calculations and clinical assessment indicate that a useful therapeutic index can be achieved with this therapy. Indium-111/yttrium-90-MX-DTPA BrE-3 can be safely administered to patients with metastatic breast cancer, and therapy doses yielded pharmacokinetics similar to those of tracer doses. Clinical responses, albeit transient, were achieved with single-dose therapy. Rapid onset of the HAMA response will hinder multicycle therapy, unless it is prevented with immunosuppressive drugs or the use of a 'humanized' antibody. Further studies are needed to determine the optimal use of BrE-3 for radioimmunotherapy.

Original languageEnglish (US)
Pages (from-to)1180-1185
Number of pages6
JournalJournal of Nuclear Medicine
Volume38
Issue number8
StatePublished - 1997

Keywords

  • BrE-3
  • Breast cancer
  • Radioimmunotherapy
  • Yttrium-90

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

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