Subclass Analysis of Malignant, Inflammatory and Degenerative Pathologies Based on Multiple Timepoint FAPI-PET Acquisitions Using FAPI-02, FAPI-46 and FAPI-74

Abstract

Purpose: FAPI-PET is a promising imaging technique for various malignant as well as non-malignant pathologies. In a recent retrospective analysis, we evaluated the diagnostic value of repetitive early FAPI-PET-imaging with FAPI-02, FAPI-46 and FAPI-74 for malignant, inflammatory/reactive and degenerative pathologies. Here, we apply a subgroup analysis to that dataset and describe the tracer-wise uptake kinetic behavior of multiple types of FAPI-positive lesions, which are encountered frequently during clinical routine. Methods: A total of 24 cancer patients underwent whole-body FAPI-PET scans, and images were acquired at 10, 22, 34, 46 and 58 min after the administration of 150–250 MBq of 68Ga-FAPI tracer molecules (eight patients each regarding FAPI-02, FAPI-46 and FAPI-74). Standardized uptake values (SUVmax and SUVmean) of healthy tissues, cancer manifestations and non-malignant lesions were measured and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition timepoints. Results: Differential uptake behavior over time was observed in several subclasses of malignant lesions, inflammatory/reactive lesions and degenerative lesions. These differences over time were particularly manifested in the direct comparison between the uptakes associated with pancreatic carcinoma (stable or increasing over time) and inflammatory lesions of the pancreas (markedly decreasing over time). Furthermore, marked differences were found between the three tracer variants regarding their time-dependent uptake and TBRs within different subclasses of malignant, inflammatory/reactive and degenerative pathologies. Conclusion: Multiple timepoint FAPI-PET/CT is a promising innovative imaging technique that provides additional imaging information compared to single timepoint imaging. Differences in the kinetic behavior of malignant and benign pathologies can facilitate the interpretation of FAPI-positive lesions.

FAP-targeted PET imaging in gastrointestinal malignancies: a comprehensive review

“…The low specificity of FAPI PET in primary tumour detection can be attributed to radiolabeled FAPI uptake in non-oncological conditions like pancreatitis and Ig4-related disease. In that matter, Pang et al demonstrated that dual time point (3-h delayed) imaging could differentiate pancreatic cancer from pancreatitis [ 61 ], supporting the similar results of Röhrich et al [ 50 ] and Glatting et al [ 65 ]. Therefore, it seems that dual time point imaging can improve the specificity of FAPI PET in primary pancreatic tumour lesions.…”

Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging

“…The reduced specificity of FAPI PET in primary tumor detection can be attributed mainly to an overlap in uptake intensity in the pancreatic primary tumor and in the tumor-induced obstructive pancreatitis of the pancreatic parenchyma [ 134 ]. Dual-time-point (3 h delayed) imaging has been investigated as a solution to distinguish between tumors and inflammation-induced fibrosis, and positive outcomes have been observed [ 20 , 21 , 135 ].…”

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation

“…Fibroblast activation protein (FAP) is a type II transmembrane glycoprotein selectively expressed on activated fibroblasts and has been found to be associated with fibrosis progression. It is worth mentioning that FAP is rarely expressed in normal fibroblasts, and meanwhile, normal tissues show relatively low uptake of FAPI. , By labeling with radionuclides such as 18 F and 68 Ga, FAPI can be specifically targeted and bind to activated fibroblasts, thereby displaying a high uptake in fibrotic tissues by positron emission tomography/computed tomography (PET/CT) in the context of some benign diseases, such as pulmonary fibrosis. , 18 F-FAPI-74 is an important PET imaging probe that has been applied in the clinic . Particularly, the application of 18 F-FAPI-74 in patients and animals has been approved by the Ethics Review Committee of our hospital.…”

“…10,11 18 F-FAPI-74 is an important PET imaging probe that has been applied in the clinic. 12 Particularly, the application of 18 F-FAPI-74 in patients and animals has been approved by the Ethics Review Committee of our hospital. Of note, 18 F-FAPI-74 has the benefit of a higher synthetic yield and a better image resolution in comparison with 68 Ga-labeled FAPI.…”