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

This longitudinal study aims to evaluate the performance of 68 Ga-FAPI-04 and 18 F-FDG and to profile the dynamic process of tumor metastasis in a preclinical 4T1 breast cancer model. Although both of these two radioligands are wildly used in clinic, no study was reported on their performance in the longitudinal monitoring of tumor metastasis. Also, no correlation between the expression level of fibroblast activation protein (FAP) and the development of tumor metastasis has been elucidated previously. In this study, we evaluated the performance of 68 Ga-FAPI-04 and 18 F-FDG PET during the entire process of tumor metastasis, and their potential for the early diagnosis of tumor metastasis. We also clarified the correlation of uptakes as well as the signal-to-background (S/B) ratios between these two probes at different stages of tumor metastasis.Methods: Forty 4T1 metastatic breast cancer murine model were established using female BALB/c mice, followed by the longitudinal imaging with 68 Ga-FAPI-04 and 18 F-FDG once a week for up to six weeks. In vitro Hematoxylin & Eosin (H&E) and immunochemistry (IHE) staining were performed to evaluate FAP expression on the metastatic lesions. Further statistical analysis was performed to evaluate the correlation of 68 Ga-FAPI-04 and 18 F-FDG uptake (%ID/cc) at different stages of the metastasis.Results: 68 Ga-FPAI-04 holds an advantage over 18 F-FDG with higher sensitivity at the early stage of tumor metastasis. However, with the progress of tumor metastasis, uptake of 68 Ga-FAPI-04 decreases and becomes less sensitive than 18 F-FDG. There is also no direct correlation between uptake or S/B ratios of 68 Ga-FAPI-04 and 18 F-FDG during this dynamic process. Conclusion:68 Ga-FAPI-04 is more sensitive than 18 F-FDG in detecting the early stage of tumor metastasis, but becomes less sensitive than 18 F-FDG at the late stage of tumor metastasis. We envision this result would be meaningful for the explanation of the 18 Ga-FAPI-04 and 18 F-FDG imaging both in the future clinic and preclinic studies.

Section: Introductionmentioning

confidence: 99%

68Ga-FAPI-04 vs. 18F-FDG in a longitudinal preclinical PET imaging of metastatic breast cancer

Ding

Huang

Liang

et al. 2021

“…At the same time, CAF-S4 promotes matrix remodelling and cancer cell invasion [59]. Moreover, Ser ing et al [33] suggested a correlation between FAPα lymph node metastases expression and lesion size (weak FAPα expression in lesion < 7 mm, which resulted negative at imaging). Therefore, we can infer that the relatively low performance of [ 68 Ga]Ga-FAPI in detecting nodal metastases reported in some studies may be related to cancer biology and the cell enrichment within lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

“…One study was designed as a phase I investigation [24]. In 12/23 studies [ 68 Ga]Ga-FAPI was offered as a compassionate drug according to the German Medicinal Product Act § 13(2b) [25,26,35,36,[27][28][29][30][31][32][33][34]. In the remaining 10/23 papers, the trial phase was not speci ed or designated as "not applicable" [37][38][39][40][41][42][43][44][45][46].…”

Section: Systematic Reviewmentioning

confidence: 99%

State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis

Sollini

Kirienko

Gelardi

et al. 2021

Introduction Fibroblast Activation Protein-α (FAPα) is overexpressed on cancer-associated broblasts in approximately 90% of epithelial neoplasms, representing an appealing target for therapeutic and molecular imaging applications. [ 68 Ga]Ga-labelled radiopharmaceuticals-FAP-inhibitors (FAPI) -have been developed for PET. We systematically reviewed and meta-analysed published literature to provide an overview of its clinical role.Materials and Methods The search, limited to January 1 st , 2018 -March 31 st 2021, was performed on MedLine and Embase databases using all the possible combinations of terms "FAP", FAPI", "PET/CT", "positron emission tomography", " broblast", "cancer-associated broblasts", "CAF", "molecular imaging", and " broblast imaging". Study quality was assessed using the QUADAS-2 criteria. Patient-based and lesion-based pooled sensitivities/speci cities of FAPI PET were computed using a random-effects model directly from the STATA "metaprop" command. Between-study statistical heterogeneity was tested (I 2statistics).Results Twenty-three studies were selected for systematic review. Investigations on staging or restaging head and neck cancer (n=2, 29 patients), abdominal malignancies (n=6, 171 patients), various cancers (n=2, 143 patients), and radiation treatment planning (n=4, 56 patients) were included in the metanalysis. On patient-based analysis, pooled sensitivity was 0.99 (95% CI 0.97-1.00) with negligible heterogeneity; pooled speci city was 0.87 (95% CI 0.62-1.00), with negligible heterogeneity. On lesion-based analysis, sensitivity and speci city had high heterogeneity (I 2 =88.56% and I 2 =97.20%, respectively). Pooled sensitivity for the primary tumour was 1.00 (95% CI 0.98-1.00) with negligible heterogeneity. Pooled sensitivity/speci city of nodal metastases had high heterogeneity (I 2 =89.18% and I 2 =95.74%, respectively). Pooled sensitivity in distant metastases was good (0.93 with 95% CI 0.88-0.97) with negligible heterogeneity.Conclusions FAPI-PET appears promising, especially in imaging cancers unsuitable for [ 18 F]FDG imaging, particularly primary lesions and distant metastases.However, high-level evidence is needed to de ne its' role, speci cally to identify cancer types, non-oncological diseases and clinical settings for its' applications.

“…Immunohistochemistry (IHC) for FAP (antibody ab207178, Abcam, 1:250) was performed on formalinfixed paraffin-embedded tissue slides according to standard IHC protocols. Immunostaining was scored as previously described [39,40]. In brief, semi-quantitative analysis of stromal staining was scored as 0 (no staining), 1 + (1-10%), 2 + (11-50%), and 3 + (51-100% stromal staining).…”

Section: Histopathological Analysismentioning

confidence: 99%

Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity – initial experience and comparison to [18F]FDG PET/CT and MRI

Linz

Brands

Kertels

et al. 2021

Purpose While [18F]-fluorodeoxyglucose ([18F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [18F]FDG and [68Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUVmax) and peak (SUVpeak) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [18F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([18F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [18F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.