Improved cancer detection in Waldeyer's tonsillar ring by ⁶⁸Ga-FAPI PET/CT imaging

Purpose: In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [¹⁸F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [¹⁸F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer's tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer's tonsillar ring, the novel PET tracer [⁶⁸Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging.

Methods: Eight patients with suspicion of a malignant tumor in Waldeyer's tonsillar ring or a CUP syndrome were examined. PET/CT scans with [¹⁸F]-FDG and [⁶⁸Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings.

Results: Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [¹⁸F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [⁶⁸Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUV_max for the primary tumors was 21.29 ± 7.97 for ¹⁸F-FDG and 16.06 ± 6.29 for ⁶⁸Ga-FAPI, respectively (p = 0.2). The mean SUV_max for the healthy contralateral tonsils was 8.38 ± 2.45 for [¹⁸F]FDG and 3.55 ± 0.47 for [⁶⁸Ga]FAPI (p < 0.001). The SUV_max ratio of [⁶⁸Ga]FAPI was significantly different from [¹⁸F] FDG (p = 0.03). Mean TBR_max for the [⁶⁸Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [¹⁸F]FDG (10.90 vs. 4.11).

Conclusion: Non-invasive imaging of FAP expression by [⁶⁸Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [¹⁸F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [⁶⁸Ga]FAPI PET/CT imaging.