Exploration of peptide T7 and its derivative as integrin αvβ3-targeted imaging agents

Abstract

Objective

The aim of the present study was to develop potential candidates of integrin αvβ3-targeted imaging agent, which can facilitate the diagnosis and treatment of malignant solid tumors.

Methods

Peptides derived from tumstatin, named T7 and T7-6H, were derivatized to contain histidine in the C-terminus of their sequence and were labeled with ^99mTc via nitrido and carbonyl precursors. The radiochemical purity and stability of ^99mTc-labeled T7 and T7-6H were characterized by thin-layer chromatography. The whole body biodistribution was studied in NCI-H157-bearing BALB/c nude mice.

Results

The ^99mTc-labeled T7 and T7-6H showed adequate in vitro stability, with a high radiochemical purity of over 90%. The dissociation constant (Kd) value of the ^99mTc-labeled T7 and T7-6H ranged from 68.5 nM to 140.8 nM in U251 and NCI-H157 cell lines. ^99mTc-labeled T7 and T7-6H showed no significant difference of biodistribution in mice. Furthermore, both T7 and T7-6H exhibited a poor blood–brain barrier penetration and a transient accumulation in lung; the uptake in tumor tissues was significantly higher than in muscle tissue, with a ratio of 5.8.

Conclusion

^99mTc-labeled T7 and T7-6H can be regarded as promising single-photon emission computed tomography probes for imaging integrin αvβ3, and need to be further studied for noninvasive detection of tumors.

Keywords:

• integrin
• angiogenesis
• ligands

Acknowledgments

The authors are thankful to Professor Tan Jian, director of the Nuclear Medicine Department, Tianjin Medical University General Hospital; and Jianfeng Liu and Dezhi Wang, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, for their support. The current work was funded by PUMC Youth Fund (grant number 2012J06) and the Development Fund of the Institute of Radiation Medicine (IRM) (grant number SF1306 and SF1418).

Disclosure

The authors report no conflicts of interest in this work.