Assessing Ultra-low Dose PET/CT and CT-less PET Using a Long Axial Field-of-view PET/CT System

Study Overview
=================
Brief Summary
-----------------
Latest generation extended axial field-of-view (FOV) PET/CT systems offer the potential for substantial reductions in applied radiopharmaceutical necessary for a clinical scan. However, such low-dose examination protocols have yet to be robustly tested or demonstrated to be non-inferior. Furthermore, extended FOV scanners offer the potential for CT-less attenuation correction of the PET emission data, making clinically acceptable ultra-low dose examination protocols with radiation exposures of < 1 millisievert possible for the first time. The aim of this study is to demonstrate the clinical acceptability of such low and ultra-low dose scanning protocols in a head-to-head prospective study against a full-dose scan using a regular FOV system

Detailed Description
-----------------
The first installation of a long-axial field-of-view (LAFOV) PET/CT system occurred in October 2020 at the department for nuclear medicine in Bern. This scanner along with recently introduced total-body scanners (TB-PET/CT) represent a substantial step forward in terms of nuclear medicine imaging technology. In conjunction with recent improvements in time-of-flight resolution and fully-digital detection technology, such systems offer surpassed sensitivity with improvements in image quality, lesion detection and diagnostic certainty. In contrast to LAFOV systems, standard axial field of view (SAFOV) scanners suffer from limited detection efficiency, where 90% of emitted photons go undetected owing to the ability to capture signal from only a small portion of the body (termed bed position or bp). However, while a number of studies are able to simulate lower applied radiopharmaceutical activities through the re-sampling of PET-sinogrammes or the rebinning of list-mode data, few studies adequately test the application of lower radiopharmaceutical activities, where limited data are available to justify the deviation from clinical routine. The clinical acceptability of such low-dose scans, in terms of lesion detection, image quality and lesion quantification is yet to be determined, which this study aims to address.

Official Title
-----------------
Assessing the Clinical Acceptability of Ultra-low Dose PET/CT and CT-less PET Using a Long Axial Field-of-view PET/CT System: a Single-centre, Single-blinded Method Agreement Study

Conditions
-----------------
PET/CT

Intervention / Treatment
-----------------
* Diagnostic Test: FD-PET/CT
* Diagnostic Test: LD-PET/CT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (>18 years) able to provide informed consent for inclusion, willing and able to undergo a PET/CT for the detection or staging of cancer. Individuals undergoing a PET/CT with 18F-FDG for the investigation of known or suspected NSCLC. Upper fasting plasma glucose levels of <8.3 mmol/L (<150 mg/dL) (as measured >30 mins prior to the administration of the radiopharmaceutical). Exclusion Criteria: Patients who are unable to consent to a second study-specific examination Patients with claustrophobia requiring medication. Patients who commence active treatment of a cancer or other pathology between scans. Patients who have not fasted for > 4 hours prior to the study. Insulin dependent diabetics.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Patients will receive first a standard of care PET/CT and then an additional low dose PET/CT. The low dose PET/CT will be reconstructed using a standard CT for attenuation correction (LD-PET/CT) and with a novel CT-less method using transmission data (ultra low dose ULD-PET/CT).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Patients will receive both a standard of care PET/CT and a low dose PET/CT | Diagnostic Test: FD-PET/CT<br>* Standard of care PET/CT with full dose (FD) of the radiopharmaceutical<br>Diagnostic Test: LD-PET/CT<br>* Additional low dose PET/CT performed within protocol defined time frame LD-PET/CT with additional ultra-low dose CT-less reconstruction<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-rater correlation coefficient | ICC for Cancer Stage using the union for international cancer control (UICC) TNM (T= tumor, N= nodal stage, M = metastasis) System (8th Edition) for low dose positron emission and computed tomography (LD-PET/CT) exams compared to the standard of care (SOC) full-dose (FD)-PET/CT as assessed by a panel of physicians | 2-6 weeks following scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-rater correlation coefficient | ICC for ultra-low dose (ULD)-PET/CT compared to FD- and LD-PET/CT | 2-6 weeks following scan | 
| Lesion uptake | Composite outcome assessing lesion quantification in terms of peak standardised uptake value (SUVpeak), tumour to background (TBR), metabolic tumour volume (MTV) and tumour glycolytic activity (TLG) for ULD- and LD-PET/CT compared to the standard of care FD-PET/CT | 2-6 weeks following scan | 
| Image quality | Composite outcome assessing image quality in terms of tumour to background ratio (TBR) and signal to noise (SNR), defined as the reciprocal coefficient of variation (COV) for ULD- and LD-PET/CT compared to the standard of care FD-PET/CT | 2-6 weeks following scan | 
| Subjective quality | Image quality (subjective) as rated by five independent nuclear medicine physicians on a five-point Likert scale (1= unacceptable, 2=poor, 3=moderate, 4=good, 5=high) for ULD- and LD-PET/CT compared to the standard of care FD-PET/CT | 2-6 weeks following scan | 
| Agreement | Inter-reader agreement for the primary outcome (UICC cancer stage) shall be compared between LD and FD-PET/CT | 2-6 weeks following scan | 
| Diagnostic accuracy | Assessment of the positive predictive value (PPV) for LD- and FD-PET/CT for patients who undergo surgery or bronchoscopy and where histopathological confirmation of true positive (TP) and false positive (FP) findings are available | 2-6 weeks following scan | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PET/CT, low dose, long-axial field-of-view, extended field-of-view, total-body PET