Evaluation of ^99mTc-HYNIC-(ser)₃-LTVPWY peptide for glioblastoma imaging

Abstract

Purpose: Early and accurate imaging of glioblastoma is of great value in staging, metastatic detection, treatment management and prognosis. The human epidermal growth factor receptor 2 (HER2) plays an essential role in the tumorigenesis and tumor progression in cancer. The aim of this study was to develop HER2-targeted peptide for glioma tumor imaging.

Material and methods: HYNIC-(Ser)₃-LTVPWY peptide was labeled with technetium-99m in presence of EDDA/tricine mixture as co-ligands. ^99mTc-HYNIC-(Ser)₃-LTVPWY peptide was assessed for cellular specific binding and receptor-binding affinity. The biodistribution study and tumor imaging were conducted in nude mice bearing U-87 MG glioma xenografts.

Results: The in vitro blocking study demonstrated specific binding of ^99mTc-HYNIC-(Ser)₃-LTVPWY in cultured U-87 MG cells with a K_D of 9.7 ± 2.0 nM. Biodistribution study revealed tumor to blood and tumor to muscle ratios were about 5.55 and 6.65 respectively after 1 h injection of radiolabeled peptide. Blocking study with non-labeled counterpart indicated a significant reduction (68%) in tumor uptake of ^99mTc-HYNIC-(Ser)₃-LTVPWY that is indicated the tumor specificity of the radiolabeled peptide on glioblastoma. Gamma planar imaging revealed that the U-87 MG tumor was clearly visualized at 1 h.

Conclusion: The results of this study showed that the ^99mTc-HYNIC-(Ser)₃-LTVPWY peptide specifically accumulates in glioma and is, therefore, a promising probe for the diagnosis of glioma.

Keywords:

• Glioma
• LTVPWY
• peptide
• 99mTc
• radiolabeled
• HER2

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported financially by Mazandaran University of Medical Sciences, Sari, Iran.

Notes on contributors

Shima Shahsavari

Shima Shahsavari, has a degree in MSc of Radiopharmaceutical Sciences, who was graduated from Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. This study was a part of her thesis.

Zahra Shaghaghi

Zahra Shaghaghi, PhD, is a researcher of radiopharmacy at the Department of Nuclear Medicine and Molecular Imaging, Clinical Development Research Unit of Farshchian Heart Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Seyed Mohammad Abedi

Seyed Mohammad Abedi, MD, is an associated professor of Nuclear Medicine at the Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Seyed Jalal Hosseinimehr

Seyed Jalal Hosseinimehr, Pharm. D, PhD, is a professor of radiopharmacy and head of the Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. He was supervisor of Shima Shahsavari for her thesis.