鎝－99m-HYNIC-Herceptin之穩定性與有效性評估：體外研究

Abstract

Background: A breast cancer with human epidermal growth factor receptor-2 (HER-2) expression usually presents rapid growth of tumor cell, high recurrence rate, poor response to traditional chemotherapy and poor survival rate. The new release of a targeted-therapy drug, Trastuzumab (Herceptin), brings the great hope to these patients. However, only 25%-30% patients with HER2 gene will response to this drug. Trastuzumab is quite expensive and has certain side effect. Therefore, it is very important to make sure if the patients have the expression of HER2 before prescription of this drug. Two common methods including immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are used for the evaluation of HER-2 expression currently. Both methods are invasive and need tissue sample from tumor via biopsy. Institute of Nuclear Energy Research (INER) has successfully developed (superscript 99m)Tc-HYNIC-Herceptin lately. There are many advantages for a scintigraphy in the evaluation of HER-2 including non-invasive, whole-body scanning, and semi-quantitative. In this study, we evaluated the in-vitro stability and effectiveness of (superscript 99m)Tc-HYNIC-Herceptin. Methods: (superscript 99m)Tc-HYNIC-Herceptin was mixed with same volume of normal saline under room temperature. Labeling efficiency at 5 mm, 30 mm, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h and 24 h was determined. The labelling efficiency at the same time points was also checked when (superscript 99m)Tc-HYNIC-Herceptin was mixed with same volume of human plasma at 37 C. (superscript 99m)Tc-HYNIC-Herceptin was mixed with BT-474 cells (high HER-2 expression human breast cancer cell) and MCF-7 cells (low HER-2 expression human breast cancer cells) and the binding of (superscript 99m)Tc-HYNIC-Herceptin to the tumor cells at 5 mm, 1 h, 4 h and 24 h was measured. Results: The labeling efficiency of (superscript 99m)Tc-HYNIC-Herceptin was greater than 90% either in normal saline or in human plasma. (superscript 99m)Tc-HYNIC-Herceptin showed high binding to BT-474 cells (70-80%) and low binding to MCF-7 cells (30- 35%). Conclusion: The (superscript 99m)Tc-HYNIC-Herceptin developed by INER has very good in-vitro stability. Its labeling efficiency can maintain above 90% even at 24 h after mixed with human plasma. In addition, (superscript 99m)Tc-HYNIC-Herceptin produced by INER can also accurately reflect the expression of HER-2 in tumor cells. These results are very encouraging and can be the good foundation for future animal study.