Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity \u2013 initial experience and comparison to [18F]FDG PET/CT and MRI

Christian Linz,Stefan Hartmann,Roman C Brands,Yingjun Zhi,Sebastian Serfling,Olivia Kertels,Malte Kircher,Alexander Kübler,Constantin Lapa,Andreas Schirbel,Andreas K Buck,Elena Gerhard-Hartmann,Alexander Dierks,Julian Hohm,Joachim Brumberg

doi:10.1007/s00259-021-05422-z

Abstract

PurposeWhile [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.MethodsTen 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.ConclusionFAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.

Highlights

Oral squamous cell carcinoma (OSCC) is the sixth most common tumor entity worldwide and the ninth most frequent cause of death [1, 2]
Since the presence of cervical lymph node (LN) metastasis is one of the most relevant negative prognostic factors [5–8] and detection of distant metastases shifts therapy from a curative to a palliative approach [9], accurate tumor staging is of paramount importance for adequate treatment choice and estimation of prognosis [10–12]
Ga-FAP inhibitors (FAPI)-04 was administered on a compassionate use basis, in compliance with §37 of Declaration of Helsinki and the German Medicinal Products Act, AMG §13 2b

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the sixth most common tumor entity worldwide and the ninth most frequent cause of death [1, 2]. With an estimated incidence of about 275,000 cases per year, it accounts for more than 90% of all malignancies of the oral cavity [3, 4]. The utility of positron emission tomography/computed tomography (PET/CT) with [18F]-fluorodeoxyglucose ([18F] FDG) for staging malignancies of the head and neck is well documented [13–18]. Specificity of [18F]FDG is hampered by uptake in inflammatory cells such as neutrophils or macrophages [19]. Since inflammatory processes are very common in head and neck tumors [20], there is an urgent need for a more specific alternative to [18F]FDG to further improve preoperative staging and therapy of OSCC

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Conclusion