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

Abstract

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18 F-FAPI PET/CT scan, the presence of FAPIavid in the fibrotic lesion was determined. Through a fibrosis rat model, 18 F-FAPI-74 was used for lesion imaging and 177 Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177 Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18 F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177 Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan−Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177 Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18 F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177 Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Cathepsin B-Activated PET Tracer for In Vivo Tumor Imaging

“…During cancer treatment, it is essential to accurately and effectively diagnose cancer at the early stage for enhancing the cure and survival rates among patients . The molecular imaging technology has made great progress in biomedical fields. , Conventional tumor imaging modalities such as computed tomography (CT), ultrasonic imaging (US), magnetic resonance imaging (MRI), positron emission tomography/single photon emission computed tomography (PET/SPECT), and optical imaging (OI) are indispensable tools for accurate diagnosis, staging, and visualization of tumors. Through these imaging technologies, accurately detecting the activity and location of cancer-related biomarkers in living tissue provides a crucial opportunity for early diagnosis of cancer.…”