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

Phase 2

Completed

Conditions: Cancer

Interventions: 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

Registration Number: NCT00375830

Lead Sponsor: Stanford University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 114

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Gadopentetate dimeglumine	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.
Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	18F-Sodium Fluoride (18F-NaF)	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.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	18F-Sodium Fluoride (18F-NaF)	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Positron Emission Tomography (PET) scan	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.
Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	18F-Fludeoxyglucose (18F-FDG)	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.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	Bone scan	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	99mTc-methyl diphosphonate	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	Whole Body Magnetic Resonance Imaging (WB-MRI) scan	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	99mTc-methyl diphosphonate	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.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	99mTc-methyl diphosphonate	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Computed Tomography (CT) scan	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Whole Body Magnetic Resonance Imaging (WB-MRI) scan	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Bone scan	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.
Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Computed Tomography (CT) scan	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.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	18F-Fludeoxyglucose (18F-FDG)	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Bone scan	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Positron Emission Tomography (PET) scan	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	18F-Sodium Fluoride (18F-NaF)	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	Positron Emission Tomography (PET) scan	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	18F-Fludeoxyglucose (18F-FDG)	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	Gadofosveset	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Gadobutrol	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.
Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan	Gadobutrol	Assessment to define the utility of 18F-NaF \& 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.
Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans	Gadofosveset	Assessment to define the accuracy of the combined 18F-NaF CT \& 18F-FDG PET/CT scan procedures compared to 99mTc MDP bone scan.

Primary Outcome Measures

Name	Time	Method
Cohort 1 - NaF PET/CT vs 99mTc-MDP Bone Scintigraphy	30 days	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").

Secondary Outcome Measures

Name	Time	Method
Cohort 1 - Detection of Osseous (Skeletal) Metastases by 18F-NaF and 18F-FDG PET/CT	30 days	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.
Cohort 1 - Whole-body MRI vs 18F-NaF PET/CT	30 days	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
Cohort 1 - Whole-body MRI vs 18F-FDG PET/CT	30 days	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.
Cohort 2 - 18F-NaF/18F-FDG vs Whole-body MRI for Detection of Skeletal Lesions	30 days	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.
Cohort 2 - 18F-NaF/18F-FDG vs 99mTc-MDP Bone Scintigraphy for Detection of Skeletal Lesions	30 days	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.
Cohort 3 - Total Skeletal Lesions Identified, Tc-99m MDP WBBS vs 18F-NaF / 18F-FDG PET/MRI	30 days	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.
Cohort 1 - 18F-NaF PET/CT vs 18F-FDG PET/CT	30 days	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.
Cohort 2 - Overall Sensitivity and Accuracy for 18F-NaF/18F-FDG vs Whole-body MRI	30 days	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.
Cohort 2 - 18F-NaF/18F-FDG PET/CT vs Whole-body MRI for Detection of Extraskeletal Lesions	30 days	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.
Cohort 2 - Overall Sensitivity and Accuracy for 18F-NaF/18F-FDG vs Whole-body MRI/99mTc-MDP Bone Scintigraphy	30 days	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.
Cohort 3 - Skeletal Lesions Identified by 99mTc MDP WBBS vs 18F-NaF / 18F-FDG PET/MRI	30 days	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.