纤维性纵隔炎(FM)是一种罕见的纵隔内增殖性疾病,可导致肺动脉高压,这被认为是死亡的主要原因。本研究旨在评价成纤维细胞活化蛋白抑制剂(FAPI)-PET/CT在纤维化大鼠FAPI靶向治疗中的潜在价值,为FM患者的临床治疗提供理论依据。通过18F-FAPIPET/CT扫描,确定了FAPI-avid在纤维化病变中的存在.通过纤维化大鼠模型,18F-FAPI-74用于病变成像,177Lu-FAPI-46用于研究体内对FM的潜在治疗作用。此外,进行了生物分布分析和辐射剂量测定。以177Lu-FAPI-46大鼠的药代动力学数据为输入,计算了成年女性的估计剂量,可以为放射性标记FAPI在患者FM检测和治疗中的安全应用提供一些有用的信息。然后,介绍了在FM中使用FAPIPET/CT和SPECT/CT的主要发现。18F-FAPI-74在患者的FM病变中显示出高水平的摄取(SUVmax7.94±0.26),这也在纤维化大鼠中观察到(SUVmax2.11±0.23)。始终如一,纤维化大鼠的SPECT/CT成像还显示,177Lu-FAPI-46-avid在纤维化病变中具有长达60小时的活性。除了这种强大的诊断性能,还评估了可能的治疗效果.结果表明,对照组没有观察到病灶的自发愈合,而在30、100和300MBq组中,第9天、第11天和第14天完全愈合,分别。Kaplan-Meier曲线中无事件发生率在四组间有显著差异(P<0.001),300MBq的剂量显示出最佳的治疗效果,肾脏未见明显损伤。此外,假定患者的器官吸收剂量和177Lu-FAPI-46的有效剂量(0.4320mSv/MBq)初步表明其在临床实践中的安全使用。总之,18F-FAPI-46PET/CT可能是诊断FM的潜在有价值的工具。值得注意的是,177Lu-FAPI-46可能是一种新型且安全的放射性标记试剂,可用于FM的诊断和治疗。
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 18F-
FAPI PET/CT scan, the presence of
FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-
FAPI-74 was used for lesion imaging and 177Lu-
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 177Lu-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. 18F-
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 177Lu-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 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-
FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.