Combined 18F-NaF/18F-FDG PET/MRI for Detection of Skeletal Metastases

Study Overview
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Brief Summary
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This clinical trial studies the use of sodium fluorine-18 (18F-NaF) plus fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/ whole body magnetic resonance imaging (WBMRI) to detect skeletal metastases in patients with stage III-IV breast cancer or stage II-IV prostate cancer.

Detailed Description
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Eligible participants had previously received a bone scan using the radiolabel 99mTc-methyl diphosphonate (t99-MDP) as part of their regular medical care. 18F-NaF and 18F-FDG are radioactive substances (radiolabels) that are absorbed by cancerous cells and allow for the cancer to be found using diagnostic procedures such as positron emission tomography (PET)/ whole body magnetic resonance imaging (WBMRI). PET/WBMRI is a combination procedure that combines the detailed PET images of areas inside the body from PET with the WBMRI scans, and may help find and diagnose skeletal metastases in patients with breast or prostate cancer. It is not yet known whether 18F-NaF/18F-FDG PET/WBMRI is better than standard imaging methods in detecting skeletal metastases. Eligible participants diagnosed with breast/prostate cancers and who have had 99mTc MDP bone scanning as part of their routine care are recruited and enrolled. Participants then receive an 18F-NaF/18F-FDG positron emission tomography (PET)/ WBMRI combination scan. The PET/MRI scans will be interpreted by 2 American Board Nuclear Medicine (ABNM)-certified physicians and 2 American Board of Radiology (ABR)-certified radiologists, all with significant clinical experience, who are blinded to the subjects' medical history and the results of other imaging modalities. The scans will be analyzed and compared against each other, with a consensus read will be obtained for each scan. Characterization of lesions as true-positive, true-negative, false-positive or false-negative will be done through a combination of clinical follow-up, imaging follow-up and/or histopathology findings. An overall diagnosis based on each scan will be determined on a 5-point scale (1=benign, 2=likely benign, 3=uncertain, 4=likely malignant, 5=malignant) to conduct a receiver operating characteristic (ROC) analysis. If the diagnosis is positive for metastases on any of the scans, the investigator will identify the number of lesions and locations of positivity, and record this information. Clinical is obtained at about 12 months after the initial scans.

Official Title
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Combined 18F-NaF/18F-FDG PET/MRI for Detection of Skeletal Metastases

Conditions
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Cancer

Intervention / Treatment
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* Procedure: Bone scan
* Drug: 99mTc-methyl diphosphonate
* Procedure: Positron Emission Tomography (PET) scan
* Drug: 18F-Fludeoxyglucose (18F-FDG)
* Procedure: Computed Tomography (CT) scan
* Drug: 18F-Sodium Fluoride (18F-NaF)
* Procedure: Whole Body Magnetic Resonance Imaging (WB-MRI) scan
* Drug: Gadopentetate dimeglumine
* Drug: Gadofosveset
* Drug: Gadobutrol


Participation Criteria
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Eligibility Criteria
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All patients were enrolled after receiving a regular medical care bone scan using the radiolabel 99mTc-methyl diphosphonate (t99-MDP). INCLUSION CRITERIA ≥ 18 years old at the time of the drug administration ≥ Stage 3 breast cancer OR ≥ stage 2 prostate cancer OR prostate-specific antigen (PSA) > 10 micrograms/L OR recurrent breast or prostate cancer Capable of complying with study procedures Able to remain still for duration of imaging procedure (about one hour) Written informed consent EXCLUSION CRITERIA Pregnant or nursing Metallic implants that contraindicate MRI Renal function impairment that contraindicates MRI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans<br>Preliminary pilot assessment to confirm feasibility & improved diagnostic accuracy of the combined 18F-NaF CT & 18F-FDG PET scan procedures, as compared to the regular medical care procedure, 99mTc MDP bone scans. | Procedure: Bone scan<br>* Scan to diagnose a number of bone conditions including cancer or metastasis<br>* Other names: Bone scintigraphy;Drug: 99mTc-methyl diphosphonate<br>* Radiolabel for bone scan procedures<br>* Other names: t99-MDP;Procedure: Positron Emission Tomography (PET) scan<br>* Scan to detect gamma rays emitted by a positron-emitting radioligand such as 18F<br>Drug: 18F-Fludeoxyglucose (18F-FDG)<br>* Radiolabel for positron emission tomography scan procedures<br>* Other names: Fluorodeoxyglucose F18;Procedure: Computed Tomography (CT) scan<br>* Scan to detect & analyze X-rays<br>* Other names: Computer-aided Tomography (CAT) scan;Drug: 18F-Sodium Fluoride (18F-NaF)<br>* Radiolabel for CT and PET scans, & as a contrast agent for MRI scans.<br>* Other names: 18F-Sodium Fluorine;Drug: Gadopentetate dimeglumine<br>* A gadolinium-based contrast agent for MRI<br>* Other names: Magnevist;|
| Experimental: Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans<br>Assessment to define the accuracy of the combined 18F-NaF CT & 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan. | Procedure: Bone scan<br>* Scan to diagnose a number of bone conditions including cancer or metastasis<br>* Other names: Bone scintigraphy;Drug: 99mTc-methyl diphosphonate<br>* Radiolabel for bone scan procedures<br>* Other names: t99-MDP;Procedure: Positron Emission Tomography (PET) scan<br>* Scan to detect gamma rays emitted by a positron-emitting radioligand such as 18F<br>Drug: 18F-Fludeoxyglucose (18F-FDG)<br>* Radiolabel for positron emission tomography scan procedures<br>* Other names: Fluorodeoxyglucose F18;Procedure: Computed Tomography (CT) scan<br>* Scan to detect & analyze X-rays<br>* Other names: Computer-aided Tomography (CAT) scan;Drug: 18F-Sodium Fluoride (18F-NaF)<br>* Radiolabel for CT and PET scans, & as a contrast agent for MRI scans.<br>* Other names: 18F-Sodium Fluorine;Procedure: Whole Body Magnetic Resonance Imaging (WB-MRI) scan<br>* Whole Body Magnetic Resonance Imaging (WB-MRI) scan: Scan that uses strong magnetic fields & radio waves to generate images of the organs in the body.<br>Drug: Gadofosveset<br>* A gadolinium-based contrast agent for MRI<br>* Other names: Ablavar;Drug: Gadobutrol<br>* A gadolinium-based contrast agent for MRI<br>* Other names: Gadavist;|
| Experimental: Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan<br>Assessment to define the utility of 18F-NaF & 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure. | Procedure: Bone scan<br>* Scan to diagnose a number of bone conditions including cancer or metastasis<br>* Other names: Bone scintigraphy;Drug: 99mTc-methyl diphosphonate<br>* Radiolabel for bone scan procedures<br>* Other names: t99-MDP;Procedure: Positron Emission Tomography (PET) scan<br>* Scan to detect gamma rays emitted by a positron-emitting radioligand such as 18F<br>Drug: 18F-Fludeoxyglucose (18F-FDG)<br>* Radiolabel for positron emission tomography scan procedures<br>* Other names: Fluorodeoxyglucose F18;Drug: 18F-Sodium Fluoride (18F-NaF)<br>* Radiolabel for CT and PET scans, & as a contrast agent for MRI scans.<br>* Other names: 18F-Sodium Fluorine;Procedure: Whole Body Magnetic Resonance Imaging (WB-MRI) scan<br>* Whole Body Magnetic Resonance Imaging (WB-MRI) scan: Scan that uses strong magnetic fields & radio waves to generate images of the organs in the body.<br>Drug: Gadofosveset<br>* A gadolinium-based contrast agent for MRI<br>* Other names: Ablavar;Drug: Gadobutrol<br>* A gadolinium-based contrast agent for MRI<br>* Other names: Gadavist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 - NaF PET/CT vs 99mTc-MDP Bone Scintigraphy | The medical value of 18F-sodium fluoride (NaF) positron emission tomography / computed tomography (PET/CT) vs 99mTc-methylene diphosphonate (MDP) bone scintigraphy was assessed on the basis of the radiation oncologist's medical assessment of image quality and detected extent of disease, for each participant. Per protocol, the data were collected and the outcome is reported for Cohort 1 only. The outcome is reported as the number of participants for whom the medical value of the image was superior for 18F-NaF vs 99mTc-MDP bone scintigraphy (18F-NaF > 99mTc-MDP), the same between both scans (18F-NaF = 99mTc-MDP), or inferior for 18F-NaF vs 99mTc-MDP bone scintigraphy (18F-NaF < 99mTc-MDP). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 - 18F-NaF PET/CT vs 18F-FDG PET/CT | The medical value of 18F-sodium fluoride (NaF) positron emission tomography / computed tomography (PET/CT) vs 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) was assessed on the basis of the radiation oncologist's medical assessment of image quality and detected extent of disease, for each participant diagnosed with osseous (skeletal) metastases. Per protocol, the data were collected and the outcome is reported for Cohort 1 only. The outcome is reported as the number of participants for whom the medical value of the image was superior for 18-NaF PET/CT compared to 18F-FDG PET/CT, the same between both scans, or inferior for 18-NaF PET/CT compared to 18F-FDG PET/CT. The outcome result is represented as a number without dispersion. | 30 days | 
| Cohort 1 - Whole-body MRI vs 18F-NaF PET/CT | The medical value of whole body magnetic imaging resonance (WB-MRI) vs 18F-sodium fluoride (NaF) positron emission tomography / computed tomography (PET/CT) was assessed on the basis of which scan detected the greater number of tumor lesions in each participant. Per protocol, the data were collected and the outcome is reported for Cohort 1 only. The outcome is reported as the number of participants for whom lesions detected by WB MRI was > 18F-NaF PET/CT; equal to 18F-NaF PET/CT; or < 18F-NaF PET/CT. The outcome result is represented as a number without dispersion. 8 analyzed 5 2 1 | 30 days | 
| Cohort 1 - Whole-body MRI vs 18F-FDG PET/CT | The medical value of whole body magnetic imaging resonance (WB-MRI) vs 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) was assessed on the basis of which scan detected the greater number of tumor lesions in each participant. Per protocol, the data were collected and the outcome is reported for Cohort 1 only. The outcome is reported as the number of participants for whom lesions detected by WB MRI was > 18F-FDG PET/CT; equal to to 18F-FDG PET/CT; or < 18F-FDG PET/CT. The outcome result is represented as a number without dispersion. | 30 days | 
| Cohort 1 - Detection of Osseous (Skeletal) Metastases by 18F-NaF and 18F-FDG PET/CT | The ability of 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) to detect osseous (skeletal) metastases was assessed. Per protocol, the data were collected and the outcome is reported for Cohort 1 only. The outcome is reported as the number of Cohort 1 participants for whom osseous metastases were detected, a number without dispersion. | 30 days | 
| Cohort 2 - 18F-NaF/18F-FDG PET/CT vs Whole-body MRI for Detection of Extraskeletal Lesions | Sensitivity; positive predictive value (PPV); and accuracy for the detection of extraskeletal lesions was assessed for 18F-sodium fluoride (NaF) / 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) and for whole body magnetic imaging resonance (WB-MRI). Sensitivity is a percentage that defines the proportion of true positive participants with the disease in a total group of participants. PPV is the probability that participants with a positive screening test truly have the disease. Accuracy is the proportion of true results (both true positives and true negatives) among the total number of cases examined. Per protocol, the data were collected and the outcome is reported for Cohort 2 only. Sensitivity, PPV, and accuracy are reported as a percentage, a number without dispersion. Higher numbers represent better detection. | 30 days | 
| Cohort 2 - 18F-NaF/18F-FDG vs Whole-body MRI for Detection of Skeletal Lesions | Sensitivity and accuracy for the detection of skeletal lesions was assessed for 18F-sodium fluoride (NaF) / 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) and for whole body magnetic imaging resonance (WB-MRI). Per protocol, the data were collected and the outcome is reported for Cohort 2 only. Sensitivity and accuracy are reported as a percentage, a number without dispersion. Higher numbers represent better detection. | 30 days | 
| Cohort 2 - 18F-NaF/18F-FDG vs 99mTc-MDP Bone Scintigraphy for Detection of Skeletal Lesions | Sensitivity and accuracy for the detection of skeletal lesions was assessed for 18F-sodium fluoride (NaF) / 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) and for 99mTc-methylene diphosphonate (MDP) bone scintigraphy. Per protocol, the data were collected and the outcome is reported for Cohort 2 only. Sensitivity and accuracy are reported as a percentage, a number without dispersion. Higher numbers represent better detection. | 30 days | 
| Cohort 2 - Overall Sensitivity and Accuracy for 18F-NaF/18F-FDG vs Whole-body MRI | Overall sensitivity and accuracy for the detection of tumor lesions was assessed for 18F-sodium fluoride (NaF) / 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) and for whole body magnetic imaging resonance (WB-MRI). Per protocol, the data were collected and the outcome is reported for Cohort 2 only. Sensitivity and accuracy are reported as a percentage, a number without dispersion. Higher numbers represent better detection. | 30 days | 
| Cohort 2 - Overall Sensitivity and Accuracy for 18F-NaF/18F-FDG vs Whole-body MRI/99mTc-MDP Bone Scintigraphy | Overall sensitivity and accuracy for the detection of tumor lesions was assessed for 18F-sodium fluoride (NaF) / 18F-fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) and for 99mTc-methylene diphosphonate (MDP) bone scintigraphy. Per protocol, the data were collected and the outcome is reported for Cohort 2 only. Sensitivity and accuracy are reported as a percentage, a number without dispersion. Higher numbers represent better detection. | 30 days | 
| Cohort 3 - Skeletal Lesions Identified by 99mTc MDP WBBS vs 18F-NaF / 18F-FDG PET/MRI | Participants in Cohort 3 received 99mTc-methylene diphosphonate (MDP) whole-body bone scintigraphy (WBBS) and 18F-sodium fluoride (NaF) / 18F-fluorodeoxyglucose (FDG) positron emission tomography / magnetic imaging resonance (PET/MRI) scans. On the basis of the scans, participants with skeletal lesions were identified. The outcome is reported as the number of Cohort 3 participants for whom skeletal lesions were identified by each scan methodology, a number without dispersion. | 30 days | 
| Cohort 3 - Total Skeletal Lesions Identified, Tc-99m MDP WBBS vs 18F-NaF / 18F-FDG PET/MRI | Participants in Cohort 3 received 99mTc-methylene diphosphonate (MDP) whole-body bone scintigraphy (WBBS) and 18F-sodium fluoride (NaF) / 18F-fluorodeoxyglucose (FDG) positron emission tomography / magnetic imaging resonance (PET/MRI) scans. On the basis of the scans, the total number skeletal lesions identified in the participants was determined. The outcome is reported as the total number skeletal lesions identified by each scan methodology, a number without dispersion. | 30 days |