“FAPI-PET: a new chapter in oncologic molecular imaging”
Year: 2025
Type: article
Abstract: Fibroblast activation protein (FAP) is a transmembrane protein with an extracellular domain made up of α/β-hydrolase and an 8-bladed β-propeller[1,2]. And it is one of the major approaches, which is utilized in PET imaging and performed in clinical practice, and focuses on targeting tumor-associated fibroblasts (TAF) by diagnosing primary or secondary tumors in the brain, liver, pancreas, or gastrointestinal tract[3]. Additionally, clinical practices also involve the administration of [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is highly sensitive and used for the diagnosis of cancer patients. However, FDG-PET is not only involved in diagnosing cancer, but it can also recognize many inflammatory activities[4]. Furthermore, FDG-PET requires the secretion of insulin intrinsically or the administration of insulin extrinsically for its absorption[5]. While the identification of tumor varieties is more limited in the case of FDG-PET, it is most favored by the administration of FAPI. Therefore, this LTE highlights the importance of FAPI-PET as a major diagnostic approach for cancer in patients. The growth of a solid epithelial tumor is correlated with an activated fibroblast cell population, which is termed Cancer-associated Fibroblast (CAF)[5]. Metabolic maintenance to tumor cells is mainly provided by CAF, recognized as microenvironmental cells[6,7]. Several markers of CAFs include tenascin-C, platelet-derived growth factor receptor-alpha/beta, CD90[8], fibroblast-specific protein 1[9], and FAP[10]. A significant role in tissue restructuring is performed by FAP through immunosuppression, drug resistance and proliferation[11]. Worse clinical outcomes have been reported in patients with high levels of FAP[12]. As a result, high FAP expression is recommended as a biomarker in specifically colon-rectal cancer (CRC) patients[13,14]. Therefore, through previous studies, FAP targeted imaging has shown strong potential towards the diagnosis of several GI cancers[3,15–17]. Consequently, FDG PET and FAPI PET have been reported to be applied in healthcare practices for the diagnosis of cancer. Frequent practices in oncology include the utilization of FDG for PET imaging. However, the application of FDG PET has its significant drawbacks. Therefore, recent techniques include the implementation of FAPI in the diagnosis of various types of cancers[3]. This can be attributed to the reduced sensitivity of FDG PET in comparison to FAPI in patients with esophageal cancers[18]. Additionally, FAPI PET shows significance over FDG PET as it offers early imaging and does not require fasting before the scan[19,20]. Furthermore, FAPI has also been reported to show strong tumor uptake after 24 hours[21]. Moreover, recent studies have also reported low FAPI background distribution with 68Ga-labeled radiotracers in comparison with several radiotracers, specifically FDG[22–24]. Consequently, recent studies report the validity of FAPI when compared with FDG. FAPI is also administered intravenously to the patient by combining it with a radionuclide (most commonly 68Ga or 18F) to produce radiopharmaceuticals[25]. Furthermore, FAPI functions independently of glucose metabolism by specifically binding to the FAP receptor through a ligand-receptor complex[3]. Although FAPI had been recommended as an advantageous method for diagnosis but it has some limitations regarding the radionuclide supply, specifically with 68Ga-labeled radiotracers. Despite the increased demand by patients, there is limited batch production of 68Ga FAPI, which does not meet the necessity. Therefore, FAPI labeled with 18F radiotracers have been produced that have a lowered positron energy, creating sharp images but shorter tumor retention in comparison with 68Ga-labeled radiotracers[26]. Additionally, 18F FAPI binds strongly to plasma proteins and hence clears from the blood slowly, which leads to FAPI being bound to normal tissues, reducing the contrast between normal tissue and the tumor. Furthermore, excretion of 18F FAPI is through the kidneys and hepatobiliary pathway, which reduces the chances of abdominal cancer detection[27]. Despite FAPI limitations, recent studies have reported the importance of FAPI through its demonstrated superiority over FDG. Therefore, the diagnosis of various types of cancers can be reported through the administration of FAPI. But, there is a need for further research to report the use of FAPI in other categories of tumors. Despite FAPI limitations, recent studies and ongoing clinical trials being conducted to use different varieties of FAPI suitable for PET imaging[28]. With FAPI demonstrating superiority over FDG, along with the requirement of suitable agents replacing PET in parts of the world where it is not commonly in practice, the development of FAPI for the diagnosis of various types of cancers is necessary[29]. Therefore, there are various factors for FAPI to show promising results and play a significant role in molecular imaging, but since it is in its early stages, more studies and clinical trials are required to report the use of FAPI in other categories of tumors. This manuscript is in compliant to TITAN Guidelines, 2025, declaring no use of AI[30].
Source: Annals of Medicine and Surgery
Authors: Muddassir Khalid, Waila Mirza, Zainab Bibi
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,850
OpenAlex ID: W7128441926