PET imaging with [68Ga]-labeled TGFβ-targeting peptide in a mouse PANC-1 tumor model

Frontiers in Oncology

Oncology

Yong Li¹  Shan Hu¹  Xichen Zhang¹  Haojian Chen¹  Hong Zhao²  Qihuang Zheng³ 

[1] Department of Nuclear Medicine, Shenzhen Hospital of Southern Medical University, Shenzhen, China;Department of Nuclear Medicine, Shenzhen People’s Hospital, Shenzhen, China;Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States;

关键词: TGFβ;    targeting peptide;    diagnostic tracer;    PET imaging;    pancreatic cancer;   

DOI  :  10.3389/fonc.2023.1228281

 received in 2023-05-24, accepted in 2023-08-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

PurposeTransforming growth factor β (TGFβ) is upregulated in many types of tumors and plays important roles in tumor microenvironment construction, immune escape, invasion, and metastasis. The therapeutic effect of antibodies and nuclide-conjugated drugs targeting TGFβ has not been ideal. Targeting TGFβ with small-molecule or peptide carriers labeled with diagnostic/therapeutic nuclides is a new development direction. This study aimed to explore and confirm the imaging diagnostic efficiency of TGFβ-targeting peptide P144 coupled with [68Ga] in a PANC-1 tumor model.ProceduresTGFβ-targeting inhibitory peptide P144 with stable activity was prepared through peptide synthesis and screening, and P144 was coupled with biological chelator DOTA and labeled with radionuclide [68Ga] to achieve a stable TGFβ-targeting tracer [68Ga]Ga-P144. This tracer was first used for positron emission tomography (PET) molecular imaging study of pancreatic cancer in a mouse PANC-1 tumor model.Results[68Ga]Ga-P144 had a high targeted uptake and relatively long uptake retention time in tumors and lower uptakes in non-target organs and backgrounds. Target pre-blocking experiment with the cold drug P144-DOTA demonstrated that the radioactive uptake with [68Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFβ-targeting specificity. [68Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect.Conclusion[68Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies.

【 授权许可】

Unknown   
Copyright © 2023 Li, Zhao, Hu, Zhang, Chen and Zheng