■成纤维细胞激活蛋白(FAP)在炎症反应和纤维化中显示出高表达。
■我们推测FAP可以作为肌腱愈合过程中的诊断和监测目标。
■对照实验室研究。
■将72只Sprague-Dawley大鼠随机分为肌腱挤压组和半部分肌腱撕裂组。每组4只大鼠手术后每周注射放射性示踪剂,持续4周,用氟化铝标记的1,4,7-三氮杂环壬烷-N,N\',N″-三乙酸缀合的FAP抑制剂(Al18F-NODA-FAPI-04)在每周的第一天施用,18F-氟脱氧葡萄糖(18F-FDG)在第二天施用。进行了小动物正电子发射断层扫描(PET)成像,术后每周收集肌腱组织进行病理和定量逆转录聚合酶链反应(qRT-PCR)分析。
■手术后一周,两种放射性示踪剂均显示病变部位的信号浓度,这是术后4周内观察到的最高放射性摄取,与病变的严重程度一致。在qRT-PCR分析期间观察到炎性细胞因子的一致趋势。此外,Al18F-NODA-FAPI-04PET显示出更精确的病变模式,归因于其对幼稚成纤维细胞的高特异性时,参考组织学发现。随着时间的推移,两种放射性示踪剂在损伤部位的摄取逐渐减少,与Al18F-NODA-FAPI-04相比,18F-FDG的下降速度更快。手术后的第四周,受损病变中Al18F-NODA-FAPI-04的最大标准化摄取值几乎回复至基线水平,表明幼稚成纤维细胞和炎症细胞的大幅减少,炎症和纤维化的减少,尤其是与第一周相比。病理和qRT-PCR结果也揭示了相应的趋势。
■我们的发现表明炎症是肌腱损伤早期的一个突出特征。Al18F-NODA-FAPI-04PET允许准确定位并提供详细的形态学成像,能够持续监测愈合进展和评估损伤严重程度。
Fibroblast activation protein (FAP) has shown high expression in inflammatory responses and fibrosis.
We speculated that FAP could serve as a diagnostic and monitoring target in the tendon healing process.
Controlled laboratory study.
A total of 72 Sprague-Dawley rats were randomly divided into a tendon crush group and a half-partial tendon laceration group. Four rats in each group were injected with radiotracers weekly for 4 weeks after surgery, with aluminum fluoride-labeled 1,4,7-triazacyclononane-N,N\',N″-triacetic acid-conjugated FAP inhibitor (Al18F-NODA-FAPI-04) administered on the first day of each week and 18F-fludeoxyglucose (18F-FDG) on the next day. Small animal positron emission tomography (PET) imaging was performed, and tendon tissue was collected for pathology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis each week after surgery.
One week after surgery, both radiotracers showed signal concentration at the lesion site, which was the highest radioactive uptake observed during 4 weeks postoperatively, consistent with the severity of the lesion. Consistent trends were observed for inflammatory cytokines during qRT-PCR analysis. Additionally, Al18F-NODA-FAPI-04 PET exhibited a more precise lesion pattern, attributed to its high specificity for naive fibroblasts when referring to histological findings. Over time, the uptake of both radiotracers at the injury site gradually decreased, with 18F-FDG experiencing a more rapid decrease than Al18F-NODA-FAPI-04. In the fourth week after surgery, the maximum standardized uptake values of Al18F-NODA-FAPI-04 in the injured lesion almost reverted to the baseline levels, indicating a substantial decrease in naive fibroblasts and inflammatory cells and a reduction in inflammation and fibrosis, especially compared with the first week. Corresponding trends were also revealed in pathological and qRT-PCR results.
Our findings suggest that inflammation is a prominent feature during the early stage of tendon injury. Al18F-NODA-FAPI-04 PET allows accurate localization and provides detailed morphological imaging, enabling continuous monitoring of the healing progress and assessment of injury severity.