[18F]FAPI-42 PET/CT in differentiated thyroid cancer: diagnostic performance, uptake values, and comparison with 2-[18F]FDG PET/CT

European Journal of Nuclear Medicine and Molecular Imaging https://doi.org/10.1007/s00259-022-06067-2 ORIGINAL ARTICLE [18F]FAPI‑42 PET/CT in differentiated thyroid cancer: diagnostic performance, uptake values, and comparison with 2‑[18F]FDG PET/CT Xingyu Mu1 · Xiaoxue Huang1 · Zewen Jiang1 · Meng Li1 · Lulu Jia1 · Zhongyuan Lv2 · Wei Fu1 · Jingsong Mao2,3 Received: 9 September 2022 / Accepted: 28 November 2022 © The Author(s) 2022 Abstract Purpose This study aimed to assess the diagnostic performance of [ 18F]FAPI-42 PET/CT and compare it with that of 2-[18F] FDG PET/CT in patients with differentiated thyroid cancer (DTC) with biochemical elevations in Tg or anti-Tg antibodies. Methods A total of 42 patients with DTC with biochemical elevations in Tg or anti-Tg antibodies underwent [ 18F]FAPI-42 PET/CT as part of this study; of which, 11 additionally underwent 2-[18F]FDG PET/CT within 7 days. Images were semiquantitatively and visually interpreted, and the quantity, location, and uptake values of lesions were noted. The diagnostic capacity of [ 18F]FAPI-42 PET/CT and biomarkers affecting the uptake of [ 18F]FAPI-42 were evaluated. In addition, the diagnostic performance and uptake of [18F]FAPI-42 and 2-[18F]FDG were compared, and the correlation between lesion diameter and quantitative parameters was investigated. Results A total of 161 lesions were detected in 27 (64%) patients on [ 18F]FAPI-42 PET/CT. FAPI-positive local recurrence showed the highest uptake intensity, followed by lymphatic, other site-associated (bone and pleura), and pulmonary lesions (mean SUVmax, 4.7 versus 3.7 versus 3.0 versus 2.2, respectively; P < 0.0001). The levels of TSH, Tg, and Tg-Ab did not affect the uptake value of lesions (median S UVmax: 2.4 versus 3.2, P = 0.56; 2.9 versus 2.4, P = 0.0935; 2.8 versus 2.6, P = 0.0525, respectively). A total of 90 positive lesions were detected in 7 patients using both modalities. All positive lesions showed statistically higher uptake of 2-[18F]FDG than that of [18F]FAPI-42 (SUVmax, 2.6 versus 2.1; P = 0.026). However, the SUVmax of [18F]FAPI-42 was higher than that of 2-[18F]FDG in local recurrences and lymphatic lesions ( SUVmax, 4.2 versus 2.9 and 3.9 versus 3.4, respectively; P > 0.05). Conclusion [18F]FAPI-42 can be used for detecting lesions and reflecting FAP expression during local recurrence and metastasis in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies. The diagnostic performance of [18F]FAPI-42 PET/CT is comparable with that of 2-[18F]FDG PET/CT in such patients. Keywords [18F]FAPI-42 · 2-[18F]FDG · Differentiated thyroid cancer · PET/CT Introduction This article is part of the Topical Collection on Oncology - Head and Neck. * Wei Fu * Jingsong Mao 1 Department of Nuclear Medicine, Affiliated Hospital, Guilin Medical University, Guilin, China 2 Department of Vascular Intervention, Affiliated Hospital, Guilin Medical University, Guilin, China 3 Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiamen 361101, China In 2020, approximately 586,000 thyroid cancer cases were reported worldwide, ranking ninth in terms of incidence [1]. Differentiated thyroid cancer (DTC) is the most common subtype, accounting for 80–85% of thyroid cancer cases, and its incidence has expended throughout recent many years [1, 2]. In spite of a generally decent prognosis, up to 30% of patients with DTC develop persistence or recurrence and 5–10% have the progressive, treatmentrefractory disease [3]. Patients with DTC with suppressed thyroglobulin (Tg) levels of ≥ 1 ng/mL, stimulated Tg levels of ≥ 10 ng/mL, or increasing Tg-Ab levels are considered to have a biochemical incomplete response after total thyroidectomy and radioiodine remnant ablation. 13 Vol.:(0123456789) European Journal of Nuclear Medicine and Molecular Imaging Approximately 20% of these patients develop structural disease, which is related to a poor prognosis [4]. Therefore, accurate and facile strategies of imaging are required for visualising local recurrences and metastatic lesions in patients with abnormal Tg or rising anti-Tg antibody levels. Cancer-associated fibroblasts (CAFs) are crucial for the growth and progression of several tumours [5, 6]. Previous studies have indicated that the expression of CAFs is profoundly connected with aggressive outcomes in DTC [7, 8]. According to the American Thyroid Association (ATA) guideline recommendations, 2-[18F]FDG PET/CT should be thought of as a recommendation in a patient with elevated Tg with negative radioactive iodine (RAI) imaging. However, this modality may not directly allow the visualisation of CAFs expression [4]. Fibroblast activation protein (FAP) is overexpressed on CAFs and rarely expressed in normal tissues. Radionuclide-labelled fibroblast activation protein inhibitor (FAPI) can be taken up by multiple types of cancers [6], including thyroid cancer. Moreover, a previous study reported promising results of FAPI-based targeted therapy in thyroid cancer [9]. However, the efficacy of [68Ga]Ga-FAPI PET/CT in detecting lesions and guiding radioligand therapy of thyroid cancer remains controversial. Some studies have suggested that low uptake values of [ 68Ga]Ga-FAPI or [ 68Ga]Ga-FAPI-negative lesions are observed in thyroid cancer [6, 10], whereas other studies have indicated that [ 68Ga]Ga-FAPI PET/CT is a promising tool for detecting metastatic thyroid cancer [9, 11–15]. Fluorine-18 (18F)-labelled ligands provide some significant advantages over the now widely used 68Ga-labeled ligands. These advantages include not only an increase in examination owing to increased production capacity but also outstanding image quality. The latter is the result of optimum tracer doses, resulting in elevated imaging statistics and 18F decay properties. The positron emission energy of 18 F is 0.6 MeV. Therefore, the distance required for positron deceleration in human tissues is significantly less than that required for 68Ga (β + energy = 2.3 MeV), which improves image resolution [16]. Furthermore, cyclotron utilisation is becoming more popular in China, and the fluorine standard has a high employment rate, which helps to promote the widespread use of such tracers [17]. Recently, several 18 F-labelled tracers targeting FAPI have been described for clinical application in various cancers [17]. However, the diagnostic performance of [ 18F]FAPI PET/CT in DTC remains unclear. Therefore, this gap impels further investigation into the clinical meaning of [18F]FAPI PET/CT in DTC and determines which part of DTC is more sensitive to [ 18F] FAPI PET/CT than other imaging modalities. The first aim of this study is to investigate the detection performance [18F]FAPI-42 PET/CT in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies, and the second aim is to compare it with that of 2-[18F] FDG PET/CT in part of patients. 13 Materials and methods Patients This study was approved by (...truncated)