Whole-Body ⁶⁸Ga-FAPI PET/CT in Cavernous Sinus Syndrome: A Prospective Comparison With ¹⁸F-FDG PET/CT

Cavernous sinus syndrome (CSS) is a clinically heterogeneous condition resulting from involvement of the cavernous sinus and its neurovascular contents. Although contrast-enhanced magnetic resonance imaging (MRI) is the imaging modality of choice for evaluating cavernous sinus pathology, it frequently cannot establish the underlying etiology because infectious, inflammatory, and neoplastic disorders often demonstrate overlapping imaging appearances. Establishing a tissue diagnosis is further complicated by the technical difficulty and potential risks associated with direct cavernous sinus biopsy. Consequently, identification of contiguous disease extension or extracranial lesions that can be safely sampled is an important component of the diagnostic work-up.

This prospective observational study evaluates the diagnostic utility of whole-body 68Ga-FAPI-46 PET/CT in adult patients with cavernous sinus syndrome in whom MRI failed to establish an etiological diagnosis. All enrolled participants undergo paired whole-body 18F-FDG PET/CT and 68Ga-FAPI-46 PET/CT prior to initiation of definitive therapy. The interval between the two PET/CT examinations does not exceed six days. MRI is performed as part of the standard diagnostic evaluation before PET/CT imaging.

The study compares the two PET tracers with respect to:

Detection of cavernous sinus lesions. Delineation of locoregional disease extension, including meningeal, pituitary/sellar, skull base, orbital, sinonasal, and adjacent soft-tissue involvement.

Detection of extracranial disease. Quantitative imaging parameters, including lesion SUVmax, background brain SUVmean, and target-to-background ratio (TBR).

Ability to identify safer and more accessible biopsy targets that may facilitate histopathological diagnosis.

PET/CT images are independently interpreted by experienced nuclear medicine physicians who are aware of the clinical presentation and MRI findings but blinded to the final diagnosis. Lesion uptake, disease distribution, and extracranial findings are assessed qualitatively, while SUVmax, background brain SUVmean, and TBR are measured for quantitative comparison. Final diagnosis is established using histopathological examination whenever feasible or established clinicoradiological diagnostic criteria when tissue confirmation is unavailable. Biopsy sites are selected following multidisciplinary discussion based on accessibility, anticipated diagnostic yield, and procedural safety. Participants are subsequently followed after initiation of etiology-directed therapy to document clinical and imaging response.

Statistical analyses include paired comparison of quantitative PET parameters using the Wilcoxon signed-rank test, comparison of lesion detection rates using the McNemar test, and comparison of quantitative imaging parameters between fungal infection and IgG4-related disease using the Mann-Whitney U test. Statistical significance is defined as a two-sided P value <0.05.