Evaluating the potential of 188Re-SOCTA-trastuzumab as a new radioimmunoagent for breast cancer treatment.

Abstract

INTRODUCTION:

Radioimmunotherapy, which utilizes monoclonal antibodies and therapeutic radioisotopes against antigen-expressing tumor tissues, is an attractive therapeutic approach for cancer therapy. Trastuzumab (Herceptin) is a humanized anti-HER-2/neu monoclonal antibody for breast cancer treatment. In this paper, we introduce a new radioimmunoagent, (188)Re-trastuzumab, via a bifunctional ligand, succinimidyl 3,6-diaza-5-oxo-3-[2-((triphenylmethyl)thio)ethyl]-8-[(triphenylmethyl)thio]octanoate (SOCTA), and evaluate its potential to be a therapeutic radiopharmaceutical for breast cancer treatment.

METHODS:

Equimolar amounts of SOCTA and trastuzumab were selected to react, and the conjugation ratio of SOCTA-trastuzumab was evaluated by the MALDI-TOF method. The immunoreactivity of SOCTA-trastuzumab was compared with nonconjugated trastuzumab in HER-2/neu overexpressing human breast cancer cell BT-474. Biodistribution experiment and microSPECT/CT images of (188)Re-SOCTA-trastuzumab being administered intravenously to SCID mice bearing xenografted BT-474 breast cancer were investigated to evaluate the tumor-targeting capability.

RESULTS:

The covalent attachment of SOCTA to trastuzumab (at 1:1 molar ratio) resulted in the averaged conjugation ratio of 0.27+/-0.06 (n=3). The complex could easily be labeled with (188)Re and achieve 95% radiochemical purity (RCP) after 1 h of reaction at room temperature. The in vitro stability study also revealed that the RCP of (188)Re-SOCTA-trastuzumab was at a value of more than 85% after 48 h of incubation with human serum. The immunoreactivity evaluation showed that SOCTA-trastuzumab and nonconjugated trastuzumab had similar binding capacity (B(max)) to HER-2/neu receptor in BT-474 cells. The animal experiments showed that (188)Re-SOCTA-trastuzumab accumulated more intensively in the tumor site as compared to normal tissue.

CONCLUSION:

We suggest that (188)Re-SOCTA-trastuzumab could be a potential candidate for radioimmunotherapy.

• Authors: Tsai-Yueh Luo, I-Chang Tang, Yu-Long Wu, Kwel-Luen Hsu, Show-Wen Liu, Hong-Chang Kung, Ping-Shan Lai, Wuu-Jyh Lin
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 36 Issue 1 Pg. 81-8 (Jan 2009) ISSN: 0969-8051 [Print] United States
• PMID: 19181272 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• 188Re-SOCTA-trastuzumab
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Cross-Linking Reagents
• Organometallic Compounds
• Radioisotopes
• epidermal growth factor receptor-neu receptor
• Rhenium
• ErbB Receptors
• Receptor, ErbB-2
• Trastuzumab

Topics

• Animals
• Antibodies, Monoclonal (chemistry, immunology, pharmacokinetics, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Breast Neoplasms (genetics, pathology, radiotherapy)
• Cell Line, Tumor
• Cross-Linking Reagents (chemistry)
• ErbB Receptors (immunology, metabolism)
• Female
• Gene Expression Regulation, Neoplastic (immunology)
• Humans
• Mice
• Organometallic Compounds (chemistry)
• Radiochemistry
• Radioimmunotherapy (methods)
• Radioisotopes
• Receptor, ErbB-2 (immunology, metabolism)
• Rhenium (chemistry)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Staining and Labeling
• Temperature
• Time Factors
• Trastuzumab