Fibroblast Activation Protein-Targeted PET/CT With Al18F-NODA-FAPI-04 for In Vivo Imaging of Tendon Healing in Rat Achilles Tendon Injury Models. 2023

Zhenfeng Liu, and Haiying Zhou, and Pengfei Li, and Zewei Wang, and Tian Tu, and Sohaib Hasan Abdullah Ezzi, and Vishnu Goutham Kota, and Mohamed Hasan Abdulla Hasan Abdulla, and Ahmad Alhaskawi, and Yanzhao Dong, and Yuqiao Huang, and Mengjie Dong, and Xinhui Su, and Hui Lu
PET Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, MMed Province, P.R. China.

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.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005355 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Cirrhosis,Fibroses
D000072078 Positron Emission Tomography Computed Tomography An imaging technique that combines a POSITRON-EMISSION TOMOGRAPHY (PET) scanner and a CT X RAY scanner. This establishes a precise anatomic localization in the same session. CT PET,CT PET Scan,PET CT Scan,PET-CT,PET-CT Scan,Positron Emission Tomography-Computed Tomography,CT PET Scans,CT Scan, PET,CT Scans, PET,PET CT Scans,PET Scan, CT,PET Scans, CT,PET-CT Scans,Scan, CT PET,Scan, PET CT,Scan, PET-CT,Scans, CT PET,Scans, PET CT,Scans, PET-CT
D000125 Achilles Tendon Tendon that connects the muscles in the back of the calf to the HEEL BONE. Calcaneal Tendon,Tendo Calcaneus,Calcaneal Tendons,Tendon, Achilles,Tendon, Calcaneal,Tendons, Calcaneal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013708 Tendon Injuries Injuries to the fibrous cords of connective tissue which attach muscles to bones or other structures. Injuries, Tendon,Injury, Tendon,Tendon Injury
D016512 Ankle Injuries Harm or hurt to the ankle or ankle joint usually inflicted by an external source. Ankle Sprains,Injuries, Ankle,Syndesmotic Injuries,Ankle Injury,Ankle Sprain,Injuries, Syndesmotic,Injury, Ankle,Injury, Syndesmotic,Sprain, Ankle,Sprains, Ankle,Syndesmotic Injury
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D049268 Positron-Emission Tomography An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower. PET Imaging,PET Scan,Positron-Emission Tomography Imaging,Tomography, Positron-Emission,Imaging, PET,Imaging, Positron-Emission Tomography,PET Imagings,PET Scans,Positron Emission Tomography,Positron Emission Tomography Imaging,Positron-Emission Tomography Imagings,Scan, PET,Tomography Imaging, Positron-Emission,Tomography, Positron Emission

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