Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

Abstract

To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.

• Authors: E L Kramer, L Liebes, C Wasserheit, M E Noz, E W Blank, A Zabalegui, J Melamed, P Furmanski, J A Peterson, R L Ceriani
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 4 Issue 7 Pg. 1679-88 (Jul 1998) ISSN: 1078-0432 [Print] United States
• PMID: 9676842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Indium Radioisotopes
• Yttrium Radioisotopes
• 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid
• Pentetic Acid

Topics

• Adult
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Breast Neoplasms (diagnostic imaging, metabolism, radiotherapy)
• Female
• Humans
• Indium Radioisotopes (pharmacokinetics, therapeutic use)
• Middle Aged
• Pentetic Acid (analogs & derivatives, pharmacokinetics, therapeutic use)
• Radioimmunotherapy (methods)
• Radiotherapy Dosage
• Tomography, Emission-Computed, Single-Photon
• Yttrium Radioisotopes (pharmacokinetics, therapeutic use)