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Increased 18F-FAPI PET/CT Uptake in a Case of Brucellosis of Lumbar Vertebral Body
Abstract
Vertebral brucellosis is a relatively rare disease that usually emerges in animal husbandry areas. We report a case that brucellosis of lumbar vertebral body showed an intense uptake of FAPI on 18F-FAPI PET/CT, which mimics to malignant lesions or vertebral tuberculosis. It is an interesting finding to realize that vertebral brucellosis is also one of the reasons for intense uptake of FAPI.
We report an adult Brodie abscess with elevated activity of ¹⁸ F-FDG and ⁶⁸ Ga-FAPI (fibroblast activating protein inhibitor), mimicking bone metastasis. Our case illustrates that Brodie abscess should also be contemplated in the differential diagnosis of osteolytic lesions with increased ⁶⁸ Ga-FAPI uptake.
A 67-year-old woman presented with dysphagia for 2 months. Enhanced chest CT suggested thickening of the esophageal wall, which was suspected to be a malignancy. The patient then underwent ¹⁸ F-FDG and ⁶⁸ Ga-FAPI PET/CT. Increased uptake was observed in both tracers in the thickened esophageal wall. However, biopsy demonstrated candida infection of esophagus. After treatment, the symptoms of the patient were relieved.
A 51-year-old woman with a history of IgA nephropathy was found to have a mass in the right lobe of the liver by abdominal ultrasound. The PET/CT scan revealed elevated ⁶⁸ Ga-FAPI-04 uptake in the aforementioned lesion, indicating the potential presence of liver cancer. However, subsequent histopathological analysis confirmed it to be an arteriovenous malformation. This case illustrates that ⁶⁸ Ga-FAPI-04 uptake can occur in arteriovenous malformation and is a benign cause of ⁶⁸ Ga-FAPI-04 uptake.
Purpose
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare inflammatory disorder of bone, joints, and skin, with various stages of bone lesions including inflammation and bone marrow fibrosis. Because the inflammation-induced fibrosis and bone marrow fibrosis are important features in SAPHO syndrome, we undertook a prospective investigation to evaluate whether PET/CT with ⁶⁸ Ga-DOTA-FAPI-04, a novel PET agent targeting fibroblast activation protein, was useful in the evaluation of the patients with SAPHO syndrome.
Patients and Methods
⁶⁸ Ga-DOTA-FAPI-04 PET/CT was performed on a cohort of 21 patients with known SAPHO syndrome. All patients underwent ⁶⁸ Ga-DOTA-FAPI-04 and ¹⁸ F-FDG PET/CT on 2 consecutive days. The positive rates of the PET/CT scans at the sites of the osteoarticular symptom, the uptake values, and agreement with clinical osteoarticular symptom were compared.
Results
A total of 38 sites of involvement were detected. ¹⁸ F-FDG PET/CT revealed 28 lesions. In contrast, ⁶⁸ Ga-DOTA-FAPI-04 PET/CT detected not only all lesions shown on ¹⁸ F-FDG PET/CT but additional 10 lesions. ⁶⁸ Ga-DOTA-FAPI-04 scan also demonstrated significantly higher uptake and target-to-background ratio than ¹⁸ F-FDG studies in the skeletal involvements. The agreement between ⁶⁸ Ga-DOTA-FAPI-04–positive lesions and current osteoarticular lesions was substantial (κ = 0.79, P < 0.001), whereas ¹⁸ F-FDG had low to moderate agreement with clinical symptoms (κ = 0.52, P < 0.001).
Conclusions
⁶⁸ Ga-DOTA-FAPI-04 has potential as a promising imaging agent for the evaluation of SAPHO syndrome.
Background
Brucellosis is an endemic systemic infectious disease, the most common complication is bone and joint involvement. Sacroiliac joint and spinal joint are the most frequently involved sites in adults, but knee joint infection is rare, and acute infectious knee arthritis complicated by acute osteomyelitis is even extremely uncommon in adults. Here, we report two cases of acute septic knee arthritis complicated by acute osteomyelitis caused by Brucella melitensis ( B. melitensis ).
Case presentation
Both patients had a history of traveling in animal husbandry areas within three months. On clinical examination, their right knee joint was tender, swollen, had limited movement and an effusion was present. Imaging examination showed effusion and synovial thickening of the right knee joint, as well as subchondral bone edema of the distal femur and proximal tibia. Laboratory examination showed that the serum agglutination test (SAT) in both patients were positive (1: 640 and 1: 320) without leukocytosis, although the proportion of lymphocytes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) significantly increased. Both patients underwent knee joint aspiration. Real-time polymerase chain reaction (Real-time PCR) analysis of synovial fluid showed that there was B. melitensis , and blood bacterial culture was negative. We determined that two patients had acute brucellosis knee arthritis complicated by acute osteomyelitis. Antibiotic treatment was given during hospitalization consisting of doxycycline (0.1 g po bid) and rifampicin (0.6 g po qd) for six weeks, and the changes of inflammatory indexes were closely monitored. At discharge, the symptoms had completely resolved, imaging abnormalities disappeared, and inflammatory indexes returned to normal. There was no recurrence of the disease at 1-year follow-up.
Conclusion
Acute brucellosis knee arthritis complicated by acute osteomyelitis is a rare but serious complication of brucellosis in adults. There is no obvious specificity of clinical manifestation and imaging examination. Early diagnosis and treatment can prevent the occurrence of knee joint deformity and even pathological fracture. Clinicians should fully consider the possibility of brucellosis where the travel or occupational history is suggestive.
Introduction and aim:
Cancer-associated fibroblasts, which are densely found in tumor tissue, express high levels of fibroblast activation protein (FAP), and FAP inhibitors (FAPIs) labeled with radionuclides can be used in the diagnosis and treatment of cancer. In this study, the role of 68Ga-DOTA-FAPI-04 PET/CT in imaging of primary, metastatic, and recurrent cancers was investigated.
Patients and methods:
A total of 42 patients (16 females, 26 males; mean age, 58.5 years; range, 31-84 years) with 22 different types of malignant diseases were included in the study. 68Ga-DOTA-FAPI-04 PET/CT imaging was performed 1 to 7 days after 18F-FDG PET/CT. Pathological uptake levels in primary tumoral lesions, lymph nodes, skeletal system, liver, peritoneal surfaces, and other body parts were compared between 2 PET/CTs. In addition, physiological uptake levels of 18F-FDG and 68Ga-FAPI were defined measuring the liver, thoracic aorta, gluteal muscle activities, and uterus activity in female patients.
Results:
Of the 42 patients in the study group, 33 patients were included for staging, 8 patients for restaging, and 1 patient for evaluation of treatment response. 68Ga-DOTA-FAPI-04 PET/CT showed intense uptake in 94.2% of primary tumoral lesions. In patients with multiple myeloma, 18F-FDG uptake in the bone marrow was significantly higher than 68Ga-FAPI uptake, whereas in gastric signet ring cell tumors, 68Ga-FAPI uptake was found to be significantly higher than 18F-FDG uptake. It was observed that 68Ga-DOTA-FAPI-04 PET/CT detected bone, liver, and peritoneum metastases with higher sensitivity and accuracy compared 18F-FDG PET/CT.
Conclusions:
The preliminary findings of this study showed that 68Ga-DOTA-FAPI-04 PET/CT can contribute to the diagnostic process in solid tumors. Especially in malignancies with mild uptake on 18F-FDG PET/CT, it stands out in diagnosis, staging, and restaging. It is also predicted that FAPI molecules can be used for radionuclide therapy in patients with metastatic disease and unresponsive to other treatments showing intense uptake on 68Ga-DOTA-FAPI-04 PET/CT.
Purpose[18F]FAPI-42 is a new fibroblast activation protein (FAP)-specific tracer used for cancer imaging. Here, we describe the optimal acquisition time and in vivo evaluation of [18F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [68Ga]Ga-FAPI-04.MethodsA total of 22 patients with various types of cancer received [18F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-h, and static 2-h scans. The in vivo biodistribution in normal organs and tumor uptake were semiquantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability.Results[18F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 min, which stayed at a similarly high level to 2 h. The optimal image acquisition time for [18F]FAPI-42 was determined to be 1 h postinjection. For tumor detection, [18F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. Compared to [68Ga]Ga-FAPI-04, [18F]FAPI-42 had the same detectability for 144 positive lesions. In addition, [18F]FAPI-42 showed a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura, and peritoneal lesions (all P < 0.05).Conclusion
The present study demonstrates that the optimal image acquisition time of [18F]FAPI-42 is 1 h postinjection and that [18F]FAPI-42 exhibits comparable lesion detectability to [68Ga]Ga-FAPI-04.Trial registrationChinese Clinical Trial Registry (ChiCTR2100045757).
A 50-year-old woman presented with back pain for 1 month. Chest CT showed osteolytic destruction of T6 vertebral body. A malignancy was suspected. The patient was subsequently enrolled in the clinical trial of 68Ga-FAPI PET/CT. 68Ga-FAPI PET/CT revealed multiple bone destruction with increased FAPI activity. It was also highly suggestive of malignancy or metastases. However, pathological examination after T6 vertebral surgery confirmed the diagnosis of tuberculous granulomatous inflammation.
A 69-year-old man presented with newly diagnosed esophageal cancer was enrolled in our clinical trial of 68Ga-FAPI PET/CT study in tumors. Increased tracer uptake was noted in esophageal cancer. In addition, the facet joint osteoarthritis of T7/8 vertebrae also revealed elevated 68Ga-FAPI uptake.
A 66-year-old woman presented with anterior chest wall and knee joints pain and multiple skin lesions. 99mTc-MDP bone scintigraphy showed increased bone density in the sternal angle with abnormal bone metabolism. The patient was enrolled in a 68Ga-DOTA-FAPI-04 PET/CT tumor clinical trial, and it showed increased tracer uptake in the sternum and right knee joint. Subsequently, ultrasound of the right knee joint confirmed the existence of synovitis, and no malignant components were found in sternal biopsy. The patient's final diagnosis was synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. The case confirmed that 68Ga-DOTA-FAPI-04 imaging is helpful for evaluating the involved sites of SAPHO syndrome.
A left pulmonary nodule was identified by CT scan in a 53-year-old woman who had a car accident 10 days earlier. 18F-FDG PET/CT showed multiple FDG-avid lesions located at the left lung nodule, mediastinal lymph nodules, and L4 vertebral body. 68Ga-FAPI PET/CT was performed for further evaluation. However, 68Ga-FAPI demonstrated intense FAPI uptake in the accident-related fracture of the L4 vertebral body. This case documents that the fracture of the vertebral body may cause FAPI uptake, and nuclear clinicians evaluating 68Ga-FAPI imaging should be aware of this potential pitfall.
The recent development of quinoline-based PET tracers that act as fibroblast-activation-protein inhibitors (FAPIs) demonstrated promising preclinical and clinical results. FAP is overexpressed by cancer-associated fibroblasts of several tumor entities. Here, we quantify the tumor uptake on 68Ga-FAPI PET/CT of various primary and metastatic tumors to identify the most promising indications for future application. Methods:68Ga-FAPI PET/CT scans were requested by various referring physicians according to individual clinical indications that were considered insufficiently covered by 18F-FDG PET/CT or other imaging modalities. All PET/CT was performed 1 h after injection of 122-312 MBq of 68Ga-FAPI-04. We retrospectively identified 80 patients with histopathologically proven primary tumors or metastases or radiologically unequivocal metastatic lesions of histologically proven primary tumors. Tumor uptake was quantified by SUVmax and SUVmean (60% isocontour). Results: Eighty patients with 28 different tumor entities (54 primary tumors and 229 metastases) were evaluated. The highest average SUVmax (>12) was found in sarcoma, esophageal, breast, cholangiocarcinoma, and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax < 6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic, and gastric cancer. The average SUVmax of hepatocellular, colorectal, head-neck, ovarian, pancreatic, and prostate cancer was intermediate (SUV 6-12). SUV varied across and within all tumor entities. Because of low background in muscle and blood pool (SUVmax < 2), the tumor-to-background contrast ratios were more than 3-fold in the intermediate and more than 6-fold in the high-intensity uptake group. Conclusion: Several highly prevalent cancers presented with remarkably high uptake and image contrast on 68Ga-FAPI PET/CT. The high and rather selective tumor uptake may open up new applications for noninvasive tumor characterization, staging examinations, or radioligand therapy.