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

نویسندگان

  • 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
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Radioimmunotherapy for breast cancer using indium-111/yttrium-90 BrE-3: results of a phase I clinical trial.

UNLABELLED 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 the...

متن کامل

Initial Clinical Evaluation of Radiolabeled MX-DTPA Humanized BrE-3 Antibody in Patients with Advanced Breast Cancer1

To evaluate radiometal-babeled humanized BrE-3 (huBrE-3) monocbonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, phannacokinetics, radiation dosimetry, and immunogenicity of “ ‘In-labeled combined 1-p-isothiocyanatobenzyl 3-methyland 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. ...

متن کامل

Biological activity of two humanized antibodies against two different breast cancer antigens and comparison to their original murine forms.

We have humanized two monoclonal antibodies (MoAbs), hu-BrE-3 and hu-Mc3, that are bound to two different antigens of the breast epithelial cell. They bind to the breast epithelial mucin (M(r) 400,000) and the BA46 antigen (M(r) 46,000). They could participate in a joint radioimmunotherapy strategy administering repeated or fractionated dosages, where increased irradiation could be delivered by...

متن کامل

Biological assessment and human absorbed dose estimation of [111In]In-DTPA-antiMUC1 as a radioimmunoconjugate for breast cancer imaging

Introduction: The aim of this study was to evaluate the human organ absorbed dose of [111In]In-DTPA-antiMUC1, as a newly developed radioimmunoconjugate. Methods: [111In]In-DTPA-antiMUC1 was prepared at optimized conditions while the radiochemical purity of the tracer was investigated using ITLC method. Biodistribution of the radiolab...

متن کامل

Preparation and preliminary studies of [64Cu]-antiMUC-1 for breast cancer targeting

PR81 is a monoclonal antibody that binds with high affinity to MUC1 that over expressed on breast tumors. PR81 is considered a suitable targeting molecule that was radiolabeled using Cu-64 for positron imaging studies. The monoclonal antibody was conjugated with DOTA moiety and after purification was evaluated for radiochemical purity, immunoreactivity, cell toxicity and structure integrity as ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 4 7  شماره 

صفحات  -

تاریخ انتشار 1998