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A 39-year-old hunter presented with chills, headache, limb pain, tachycardia, hypertension, ventricular extrasystoles, elevated inflammatory values, and persistent chest pain. A CT scan revealed a mass on the left hilus (A). Due to suspicion of lymphoma or lung cancer 1 week later, an 18FDG (B–D) plus a 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT scan (E–G) were performed. The hilar mass increased in size (B, E) and demonstrated both intense 18FDG uptake (SUVmax 24.5) (C, D) and 68 Ga-FAPI accumulation (SUVmax 23.2) (F, G) strongly indicating malignancy. However, subsequent EBUS-TBNA and EUS-B yielded necrotizing granulomatosis (H). Finally, a bone-hard mass on the left hilus discharging creamy pus was resected by VATS. Pathological and microbiological workup evidenced Francisella tularensis infection by FISHseq analysis (Fluorescence in situ hybridization combined with 16S rRNA gene amplification and sequencing [1]), ELISA, and Western blot. Postoperative bronchoscopy demonstrated re-established bronchus patency (I). After antibiotic therapy with gentamicin and ciprofloxacin, no recurrence was detectable on CT control 20 weeks later (J).
18FDG PET/CT is one of the diagnostic mainstays in oncology and standard imaging in patients with lung mass. However, its specificity is impaired due to inflammation-induced uptake. In tularemia, a granulomatous inflammation, 18FDG PET/CT revealed an uptake pattern indicative for lung cancer in more than 50% of all cases [2]. 68Ga-FAPI emerged as an alternative tracer for tumor imaging, as FAP is expressed in > 90% of epithelial cancers [3, 4]. 68Ga-FAPI shows high uptake and tumor-to-background ratio in primary lung cancer and in metastatic lesions of other tumor types located in the lung [5,6,7,8,9]. Although promising data on this new radiotracer are increasing, false-positive results in non-malignant diseases with FAP uptake have been reported [10]. Also, chronic infections like tuberculosis might occasionally demonstrate increased 68Ga-FAPI [11]. On the other hand, in a head-to-head comparison (sub)acute inflammation in lymph nodes after COVID-19 vaccination induces no 68Ga-FAPI accumulation besides a positive FDG signal [12].
Our case adds tularemia to the scope of potential granulomatous inflammation-induced pitfalls in hybrid imaging coming along with increased high FDG uptake but also high FAP expression. However, given an already known diagnosis of granulomatous disease like tularemia, 68Ga-FAPI PET/CT might be suitable to assess extent and activity of chronic inflammation.
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Wolfgang P. Fendler reports fees from SOFIE Bioscience (research funding), Janssen (consultant, speaker), Calyx (consultant), Bayer (consultant, speaker, research funding), Parexel (image review), Novartis (speaker), and Telix (speaker) outside of the submitted work. Benedikt M. Schaarschmidt received a research grant from PharmaCept for an undergoing investigator-initiated study not related to this paper. Ken Herrmann reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, personal fees from Debiopharm, personal fees from AstraZeneca, personal fees from Janssen, outside the submitted work. Mathias Meetschen was supported as a Junior Clinician Scientist within the University Medicine Essen Academy (UMEA) program. Annette Moter reports honoraria for lectures by BioMerieux and Chiesi and holds shares in MoKi Analytics GmbH and Moter Diagnostics private practice.
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This is a case presentation of the ongoing 68Ga-FAPI PET observational trial conducted at the University Hospital Essen (NCT04571086). Evaluation of data was approved by the ethics committee of the University Duisburg-Essen (20–9485-BO and 19–8991-BO).
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Meetschen, M., Sandach, P., Darwiche, K. et al. Rabbit fever: granulomatous inflammation by Francisella tularensis mimics lung cancer in dual tracer 18FDG and 68Ga-FAPI PET/CT. Eur J Nucl Med Mol Imaging 50, 2567–2569 (2023). https://doi.org/10.1007/s00259-023-06175-7
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DOI: https://doi.org/10.1007/s00259-023-06175-7