99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging

Sajjad Ahmadpour,Zohreh Noaparast,Seyed Jalal Hosseinimehr,Seyed Mohammad Abedi

doi:10.1186/s12929-018-0420-x

Sajjad Ahmadpour, Zohreh Noaparast + Show 2 more

Open Access

https://doi.org/10.1186/s12929-018-0420-x

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Abstract

BackgroundBreast 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.MethodsThe 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.ResultsRadiochemical 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.ConclusionsThe 99mTc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.

Highlights

Breast cancer is the most common malignancy among women in the world
FROP-1 peptide consists of Glu1-As2-Tyr3-Glu4-Leu5-Met6-Asp7-Leu8Leu9-Ala10-Tyr11-Leu12 amino acids that significantly has ability binding to the various type of the cancer cell lines, especially thyroid cancer cells FRO82–2 and MCF-7 breast cancer cells
Radiochemical assessments HYNIC-Lys-FROP (Fig. 1) was labeled efficiently with 99mTc by a ligand exchange method with a radiochemical purity of 99.6% which was determined with instant thin layer chromatography (ITLC) method

Summary

Introduction

Breast cancer is the most common malignancy among women in the world. In this study we developed 99mTc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. Breast cancer is the second most common malignancy with high risk of metastasis and death among women in the world [1]. The 5-year survival rate for women diagnosed with metastatic breast cancer is only about 27.4% [2]. The early detection can dramatically improve the survival rate of breast cancer patients [3]. A 12-amino-acid FROP-1 peptide as tumor cell binding peptide was identified through phage display system by Sabine Zitzmann research group [13]. FROP-1 peptide consists of Glu1-As2-Tyr3-Glu4-Leu5-Met6-Asp7-Leu8Leu9-Ala10-Tyr11-Leu amino acids that significantly has ability binding to the various type of the cancer cell lines, especially thyroid cancer cells FRO82–2 and MCF-7 breast cancer cells. This research group labeled FROP-1 peptide with iodide radioisotopes (131I and 125I) [13] and 111In radionuclide [14] for in vitro and in vivo evaluation of FROP-1 binding to MCF-7 cell line

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Conclusion