Head-to-head Comparison of Positron Nuclide Radio-labeled FAPI and 18F-FDG PET/CT in Patients With Malignant Tumors

At the beginning of 2022, the National Cancer Center released the latest statistical data showing that the incidence rate of malignant tumors in China reached 293.91/100000, and the mortality rate reached 174.55/100000 [1]. Malignant tumors have become an important public health issue affecting the health of Chinese residents, bringing a heavy economic burden to the public health system. Different from the cancer spectrum in developed countries, digestive system tumors with poor prognosis in China, such as lung cancer, liver cancer, stomach cancer, intestinal cancer, and esophageal cancer, are at a high incidence, while those with good prognosis in European and American developed countries are at a high incidence, such as thyroid cancer, breast cancer and prostate cancer; Even the 5-year survival rate of thyroid cancer, breast cancer and prostate cancer with good prognosis still lags behind that of developed countries such as the United States [2,3]. The main reason for this is the low number of early cases, low early diagnosis rate, and non-standard clinical diagnosis and treatment of late cases. Therefore, early detection, diagnosis, staging, and intervention have become urgent issues to be addressed.

Malignant tumors often have insidious onset and overlapping symptoms; Most patients are discovered by chance, and when clinical symptoms and signs are more obvious, patients are often in the late clinical stage. Relying solely on serum tumor markers for diagnosis may result in certain false positives and false negatives [5]. Imaging examination is the preferred and non-invasive evaluation method for malignant tumors, with the advantages of being intuitive and simple. Ultrasound imaging has the advantages of non-invasive, convenient, and high accuracy in the diagnosis of superficial organs such as the thyroid, breast, and liver. However, the detection results are greatly influenced by the examiner\'s experience, and the repeatability is poor. Its application in staging, efficacy evaluation, and prognosis follow-up is limited. CT and MR scans can provide detailed and accurate anatomical information for identifying the location of the primary lesion, local and distant metastases, and are crucial for determining the optimal surgical plan and treatment selection [6]. However, the accuracy of anatomical imaging is limited by the size and morphology of the lesion, and small lesions are prone to misdiagnosis. In addition, some malignant tumor lesions have concealment, making them difficult to detect and diagnose.

The emergence of functional imaging devices has made real-time fusion of anatomical structures and functional/metabolic/biochemical images possible. Positron emission computed tomography/X-ray computed tomography (PET/CT) uses specific molecular probes to target tumor visualization. It can provide detailed information on the biochemical changes of tumor tissue at the cellular and molecular levels, with better sensitivity and specificity compared to traditional imaging methods, achieving the goal of accurate diagnosis [7-9]. 18F-FDG is currently the most widely used positron imaging agent in clinical practice, with good sensitivity and specificity for lung cancer. 18F-FDG is not a tumor-specific imaging agent and is susceptible to interference from patient eating and blood glucose levels; Before examination, the patient needs to have an empty stomach for at least 6 hours, and the blood sugar level needs to be lower than 11.0mmol/L, which is difficult for some diabetes patients to tolerate. The physiological uptake of brain, myocardium, intestinal mucosa, infected tissue, or inflammatory cells can lead to high uptake of 18F-FDG, resulting in a significant increase in false positive rates; In addition, some tumors, such as well-differentiated hepatocellular carcinoma, renal cell carcinoma, and signet ring cell carcinoma, have a low uptake rate of 18F-FDG and a high false negative rate. Therefore, developing new tumor-targeted molecular probes is very important [10,11].

The latest research found that in tumor tissues, especially epithelial tumors, such as ovarian cancer, gastric cancer, lung cancer, and breast cancer, the tumor matrix fibroblast membrane highly expresses fibroblast activation protein (FAP), which is a type II transmembrane serine protease [12,13]. It is worth noting that the liver, ovaries, pancreas, and stomach hardly exhibit FAP activity under normal conditions, but after carcinogenesis, the expression level of FAP is significantly increased. Therefore, based on the upregulation and selective expression of FAP after normal tissue carcinogenesis, it has been identified as a potential biomarker for tumor-associated fibroblasts [14]. In recent years, foreign scholars have achieved very good results in using positron-labeled FAP inhibitors to target FAP and display tumor stroma. Although the studies were based on small sample data or case reports, they achieved significantly better results than 18F-FDG [13,15-17]. Therefore, further multi-case and head-to-head studies with 18F-FDG are necessary for various malignant tumors.

Therefore, this study used an intra-individual control to compare the head-to-head comparison between positron-labeled fibroblast activation protein inhibitors and 18F-FDG PET/CT in detecting primary and metastatic lesions of malignant tumors.