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

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.