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

October 29, 2026 updated by: Rajender Kumar, Post Graduate Institute of Medical Education and Research, Chandigarh

The goal of this observational study is to evaluate the diagnostic utility of whole-body ⁶⁸Ga-FAPI PET/CT in adults with cavernous sinus syndrome (CSS) in whom magnetic resonance imaging (MRI) failed to establish the underlying cause. The study also compares the performance of ⁶⁸Ga-FAPI PET/CT with paired ¹⁸F-FDG PET/CT.

The main questions it aims to answer are:

Can whole-body ⁶⁸Ga-FAPI PET/CT detect and characterize cavernous sinus lesions and disease extent in patients with MRI-indeterminate CSS? Does ⁶⁸Ga-FAPI PET/CT provide superior lesion conspicuity and help identify safer biopsy sites compared with ¹⁸F-FDG PET/CT? Researchers will compare whole-body ⁶⁸Ga-FAPI PET/CT with paired ¹⁸F-FDG PET/CT to evaluate lesion detection, quantitative imaging parameters, disease extent, and their impact on identifying appropriate biopsy targets.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Chandigarh
      • Chandigarh, Chandigarh, India, 160012
        • Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh 160012

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population consisted of consecutive adult patients presenting with clinically diagnosed cavernous sinus syndrome (CSS) at a tertiary care academic referral center between January 2023 and May 2024. Eligible participants had contrast-enhanced MRI demonstrating cavernous sinus pathology but without a definitive etiological diagnosis. All participants underwent paired whole-body ¹⁸F-FDG PET/CT and ⁶⁸Ga-FAPI-46 PET/CT prior to initiation of definitive therapy as part of the diagnostic evaluation.

Description

Inclusion Criteria:

  • Adults aged 18 years or older.
  • Clinical diagnosis of cavernous sinus syndrome (CSS), defined as involvement of two or more cranial nerves (III, IV, V1, V2, or VI) on the same side, or involvement of a single cranial nerve in the presence of a radiologically confirmed cavernous sinus lesion.
  • Contrast-enhanced MRI demonstrating cavernous sinus pathology but failing to establish a definitive etiological diagnosis.
  • Ability and willingness to provide written informed consent.
  • Not receiving definitive etiology-directed therapy before completion of both PET/CT examinations.

Exclusion Criteria:

  • Pregnant or lactating women.
  • Unwilling or unable to provide written informed consent.
  • Uncontrolled hyperglycemia precluding performance of ¹⁸F-FDG PET/CT.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: CASE_ONLY
  • Time Perspectives: PROSPECTIVE

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
adult patients with cavernous sinus syndrome in whom MRI failed to establish etiological diagnosis
Diagnostic test: FAPI tracer

Pilot study evaluating the role of FAPI PET/CT in Cavernous sinus syndrome

Drug: FDG-PET

Whole-body ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT performed after at least 6 hours of fasting and confirmation of blood glucose <200 mg/dL. ¹⁸F-FDG was administered intravenously at a dose of 3.7 MBq/kg body weight. Imaging was acquired approximately 60 minutes after tracer injection from the vertex to mid-thigh with an additional dedicated brain acquisition. This served as the comparator imaging modality for paired evaluation with ⁶⁸Ga-FAPI-46 PET/CT.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Diagnostic performance of ⁶⁸Ga-FAPI PET/CT for detection of cavernous sinus lesions compared with paired ¹⁸F-FDG PET/CT
Time Frame: Baseline (prior to initiation of definitive therapy; both PET/CT examinations performed within 6 days of each other).

Comparison of cavernous sinus lesion detection rates between whole-body ⁶⁸Ga-FAPI PET/CT and paired ¹⁸F-FDG PET/CT on a lesion basis using the McNemar test. A lesion is considered positive when tracer uptake exceeds adjacent background
Baseline (prior to initiation of definitive therapy; both PET/CT examinations performed within 6 days of each other).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison of lesion target-to-background ratio (TBR) between ⁶⁸Ga-FAPI PET/CT and ¹⁸F-FDG PET/CT
Time Frame: Baselines

Comparison of lesion TBR calculated as lesion SUVmax divided by background brain SUVmean for paired lesions.
Baselines
Comparison of lesion SUVmax between ⁶⁸Ga-FAPI PET/CT and ¹⁸F-FDG PET/CT
Time Frame: Baseline

Comparison of maximum standardized uptake value (SUVmax) of paired cavernous sinus lesions between the two PET tracers.
Baseline
Proportion of participants in whom ⁶⁸Ga-FAPI PET/CT identified an alternative biopsy site
Time Frame: Baseline

Percentage of participants in whom whole-body ⁶⁸Ga-FAPI PET/CT identified a safer and more accessible contiguous or extracranial lesion suitable for tissue diagnosis instead of direct cavernous sinus biopsy.
Baseline
Detection of clinically relevant extracranial disease by whole-body ⁶⁸Ga-FAPI PET/CT
Time Frame: Baseline

Number of participants with disease-related extracranial lesions identified on whole-body ⁶⁸Ga-FAPI PET/CT
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Post Graduate Institute of Medical Education and Research, Chandigarh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2025

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 29, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 5, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ChandigarhPGIMER1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings