Evaluation of a CD13 and Integrin αvβ3 Dual-Receptor Targeted Tracer 68Ga-NGR-RGD for Ovarian Tumor Imaging: Comparison With 18F-FDG

Yu Long; Fuqiang Shao; Hao Ji; Xiangming Song; Xiaoying Lv; Xiaotian Xia; Qingyao Liu; Yongxue Zhang; Dexing Zeng; Xiaoli Lan; Yongkang Gai

doi:10.3389/fonc.2022.884554

Evaluation of a CD13 and Integrin α_vβ₃ Dual-Receptor Targeted Tracer ⁶⁸Ga-NGR-RGD for Ovarian Tumor Imaging: Comparison With ¹⁸F-FDG

Front Oncol. 2022 May 18:12:884554. doi: 10.3389/fonc.2022.884554. eCollection 2022.

Authors

Yu Long^{1

2}, Fuqiang Shao^{1

2}, Hao Ji^{1

2}, Xiangming Song^{1

2}, Xiaoying Lv^{1

2}, Xiaotian Xia^{1

2}, Qingyao Liu^{1

2}, Yongxue Zhang^{1

2}, Dexing Zeng³, Xiaoli Lan^{1

2}, Yongkang Gai^{1

2}

Affiliations

¹ Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
³ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States.

Abstract

Ovarian cancer has the highest mortality rate of gynecologic malignancy. ¹⁸F-FDG positron emission tomography (PET) adds an important superiority over traditional anatomic imaging modalities in oncological imaging but has drawbacks including false negative results at the early stage of ovarian cancer, and false positives when inflammatory comorbidities are present. Aminopeptidase N (APN, also known as CD13) and integrin α_vβ₃ are two important targets overexpressed on tumor neo-vessels and frequently on ovarian cancerous cells. In this study, we used subcutaneous and metastatic models of ovarian cancer and muscular inflammation models to identify ⁶⁸Ga-NGR-RGD, a heterodimeric tracer consisting of NGR and RGD peptides targeting CD13 and integrin α_vβ₃, respectively, and compared it with ¹⁸F-FDG. We found that ⁶⁸Ga-NGR-RGD showed greater contrast in SKOV3 and ES-2 tumors than ¹⁸F-FDG. Low accumulation of ⁶⁸Ga-NGR-RGD but avid uptake of ¹⁸F-FDG were observed in inflammatory muscle. In abdominal metastasis models, PET imaging with ⁶⁸Ga-NGR-RGD allowed for rapid and clear delineation of both peritoneal and liver metastases (3-6 mm), whereas, ¹⁸F-FDG could not distinguish the metastasis lesions due to the relatively low metabolic activity in tumors and the interference of intestinal physiological ¹⁸F-FDG uptake. Due to the high tumor-targeting efficacy, low inflammatory uptake, and higher tumor-to-background ratios compared to that of ¹⁸F-FDG, ⁶⁸Ga-NGR-RGD presents a promising imaging agent for diagnosis, staging, and follow-up of ovarian tumors.

Keywords: CD13; dual-receptor targeted; integrin αvβ3; ovarian cancer; positron emission tomography (PET).