Samaneh Abbasi - Department of Medical Physics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Sara Khademi - Department of Radiology Technology, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
Alireza Montazerabadi - Department of Medical Physics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Amirhossein Sahebkar - Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India

Background: Fibroblast Activation Protein (FAP)-targeted nanoparticles (NPs) are designed to accumulate in cancerous stroma. These NPs hold promise for imaging applications in cancer therapy.Objective: This systematic review aimed to comprehensively explore the use of FAP-targeting NPs for cancer diagnosis through different imaging modalities.Material and Methods: This systematic review followed the framework proposed by O’Malley and Arksey. Peer-reviewed studies were searched in the Scopus, Science Direct, PubMed, and Google Scholar databases. Eligible studies were selected, and data were extracted to investigate the FAP-targeting NPs in imaging. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was also utilized to present the results.Results: Five studies met the specified inclusion criteria and were finally selected for analysis. The extracted data was classified into two categories: general and specific data. The general group indicated that most studies have been conducted in Mexico and have increased since ۲۰۲۲, and the specific group showed that colorectal cancer and Nude mice have received the most research attention. Furthermore, FAP-targeted NPs have demonstrated superior diagnostic imaging capabilities, even compared to specific methods for each cancer type. Also, they have been safe, with no toxicity. Conclusion: FAP-targeted NPs using different ligands, such as Fibroblast Activation Protein Inhibitor (FAPI), can accurately detect tumors and metastases, and outperform specific cancer peptides like PSMA in cancer diagnosis. They are also non-toxic and do not cause radiation damage to tissues. Therefore, FAP-targeted NPs have the potential to serve as a viable alternative to FAP-targeted radionuclides for cancer diagnosis.

Neoplasms, Fibroblast Activation Protein (FAP), Imaging, Nanoparticles (NPs), Molecular imaging