- 作者: Sajjad Ahmadpour, Zohreh Noaparast, Seyed Mohammad Abedi and Seyed Jalal Hosseinimehr
- 作者服務機構: 1. Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
- 中文摘要:
- 英文摘要:
Background
Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99mTc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor.
Methods
The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99mTc using tricine/EDDA co-ligand. The cellular specific binding of 99mTc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice.
Results
Radiochemical purity for 99mTc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (Kd) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99mTc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99mTc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i.
Conclusions
The 99mTc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells. - 中文關鍵字:
- 英文關鍵字: Breast cancer, MCF-7, Tumor targeting, Imaging, FROP, Radiopharmaceutica