Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent

Title:Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent

Volume: 18 Issue: 2

Author(s): Mohsen Mohammadgholi, Nourollah Sadeghzadeh*, Mostafa Erfani, Saeid Abediankenari, Seyed Mohammad Abedi, Iman Emrarian, Narjes Jafari and Ramezan Behzadi

Affiliation:

• Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari,Iran

Keywords: Aptide, fibronectin extra-domain B, HYNIC, phage display, radiolabelling, technetium-99m, tumour imaging agent, APTEDB.

Abstract: Background: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB.

Objective: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling.

Methods: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT.

Results: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one.

Conclusion: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection.

Cite this article as:

Mohammadgholi Mohsen , Sadeghzadeh Nourollah *, Erfani Mostafa , Abediankenari Saeid , Abedi Mohammad Seyed , Emrarian Iman , Jafari Narjes and Behzadi Ramezan , Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (2) . https://dx.doi.org/10.2174/1871520617666170918125020