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

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: 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); Drug: Gadopentetate dimeglumine; Procedure: Whole Body Magnetic Resonance Imaging (WB-MRI) scan; Drug: Gadofosveset; Drug: Gadobutrol

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.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Pilot-WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans; 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; Scan to diagnose a number of bone conditions including cancer or metastasis; Other Names: Bone scintigraphy; Drug: 99mTc-methyl diphosphonate; Radiolabel for bone scan procedures; Other Names: 99mTc-MDP; 99mTc-methylene diphosphonate; Technetium 99mTc medronate; t99-MDP; Procedure: Positron Emission Tomography (PET) scan; Scan to detect gamma rays emitted by a positron-emitting radioligand such as 18F; Drug: 18F-Fludeoxyglucose (18F-FDG); Radiolabel for positron emission tomography scan procedures; Other Names: Fluorodeoxyglucose F18; 2-Deoxy-2-(18F)Fluoro-D-Glucose; 2-F18-Fluoro-2-deoxy-D-glucose; 2-F18-Fluoro-2-deoxyglucose; 18F 2-Fluoro-2-deoxy-D-Glucose; Fludeoxyglucose F-18; Procedure: Computed Tomography (CT) scan; Scan to detect & analyze X-rays; Other Names: Computerized Axial Tomograph (CAT) scan; Computer-aided Tomography (CAT) scan; Drug: 18F-Sodium Fluoride (18F-NaF); Radiolabel for CT and PET scans, & as a contrast agent for MRI scans.; Other Names: 18F-Sodium Fluorine; Drug: Gadopentetate dimeglumine; A gadolinium-based contrast agent for MRI; Other Names: Magnevist
Experimental: Cohort 2 WB-MRI & Combined 18F-NaF-CT/18F-FDG-PET scans; 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; Scan to diagnose a number of bone conditions including cancer or metastasis; Other Names: Bone scintigraphy; Drug: 99mTc-methyl diphosphonate; Radiolabel for bone scan procedures; Other Names: 99mTc-MDP; 99mTc-methylene diphosphonate; Technetium 99mTc medronate; t99-MDP; Procedure: Positron Emission Tomography (PET) scan; Scan to detect gamma rays emitted by a positron-emitting radioligand such as 18F; Drug: 18F-Fludeoxyglucose (18F-FDG); Radiolabel for positron emission tomography scan procedures; Other Names: Fluorodeoxyglucose F18; 2-Deoxy-2-(18F)Fluoro-D-Glucose; 2-F18-Fluoro-2-deoxy-D-glucose; 2-F18-Fluoro-2-deoxyglucose; 18F 2-Fluoro-2-deoxy-D-Glucose; Fludeoxyglucose F-18; Procedure: Computed Tomography (CT) scan; Scan to detect & analyze X-rays; Other Names: Computerized Axial Tomograph (CAT) scan; Computer-aided Tomography (CAT) scan; Drug: 18F-Sodium Fluoride (18F-NaF); Radiolabel for CT and PET scans, & as a contrast agent for MRI scans.; Other Names: 18F-Sodium Fluorine; Procedure: Whole Body Magnetic Resonance Imaging (WB-MRI) scan; 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.; Drug: Gadofosveset; A gadolinium-based contrast agent for MRI; Other Names: Ablavar; Drug: Gadobutrol; A gadolinium-based contrast agent for MRI; Other Names: Gadavist
Experimental: Cohort 3 Combined 18F-NaF / 18F-FDG PET/WB-MRI scan; Assessment to define the utility of 18F-NaF & 18F-FDG as the radiolabels in a single combined PET / WB-MRI procedure.	Procedure: Bone scan; Scan to diagnose a number of bone conditions including cancer or metastasis; Other Names: Bone scintigraphy; Drug: 99mTc-methyl diphosphonate; Radiolabel for bone scan procedures; Other Names: 99mTc-MDP; 99mTc-methylene diphosphonate; Technetium 99mTc medronate; t99-MDP; Procedure: Positron Emission Tomography (PET) scan; Scan to detect gamma rays emitted by a positron-emitting radioligand such as 18F; Drug: 18F-Fludeoxyglucose (18F-FDG); Radiolabel for positron emission tomography scan procedures; Other Names: Fluorodeoxyglucose F18; 2-Deoxy-2-(18F)Fluoro-D-Glucose; 2-F18-Fluoro-2-deoxy-D-glucose; 2-F18-Fluoro-2-deoxyglucose; 18F 2-Fluoro-2-deoxy-D-Glucose; Fludeoxyglucose F-18; Drug: 18F-Sodium Fluoride (18F-NaF); Radiolabel for CT and PET scans, & as a contrast agent for MRI scans.; Other Names: 18F-Sodium Fluorine; Procedure: Whole Body Magnetic Resonance Imaging (WB-MRI) scan; 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.; Drug: Gadofosveset; A gadolinium-based contrast agent for MRI; Other Names: Ablavar; Drug: Gadobutrol; A gadolinium-based contrast agent for MRI; Other Names: Gadavist

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Andrei Iagaru, MD, Stanford University

Publications and helpful links

General Publications

• Iagaru A, Young P, Mittra E, Dick DW, Herfkens R, Gambhir SS. Pilot prospective evaluation of 99mTc-MDP scintigraphy, 18F NaF PET/CT, 18F FDG PET/CT and whole-body MRI for detection of skeletal metastases. Clin Nucl Med. 2013 Jul;38(7):e290-6. doi: 10.1097/RLU.0b013e3182815f64.
• Minamimoto R, Loening A, Jamali M, Barkhodari A, Mosci C, Jackson T, Obara P, Taviani V, Gambhir SS, Vasanawala S, Iagaru A. Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer. J Nucl Med. 2015 Dec;56(12):1862-8. doi: 10.2967/jnumed.115.162610. Epub 2015 Sep 24.
• Iagaru A, Minamimoto R, Jamali M, Barkodhodari A, Gambhir SS, Vasanawala S. Imaging patients with breast and prostate cancers using combined 18F NaF/18F FDG and TOF simultaneous PET/ MRI. EJNMMI Phys. 2015 Dec;2(Suppl 1):A65. doi: 10.1186/2197-7364-2-S1-A65. No abstract available.
• Sonni I, Minamimoto R, Baratto L, Gambhir SS, Loening AM, Vasanawala SS, Iagaru A. Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F] F and [18F]FDG: a Focus on Skeletal Lesions. Mol Imaging Biol. 2020 Apr;22(2):397-406. doi: 10.1007/s11307-019-01392-9.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2006
• Primary Completion (Actual): April 17, 2017
• Study Completion (Actual): March 14, 2019

Study Registration Dates

• First Submitted: September 11, 2006
• First Submitted That Met QC Criteria: September 11, 2006
• First Posted (Estimated): September 13, 2006

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: November 18, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Protective Agents; Radiopharmaceuticals; Bone Density Conservation Agents; Cariostatic Agents; Fluorodeoxyglucose F18; Listerine; Fluorides; Sodium Fluoride; Deoxyglucose; Methylene diphosphonate; Technetium Tc 99m Medronate; Diphosphonates
• Other Study ID Numbers: IRB-03778; 96754 (Other Identifier: Stanford University Alternate IRB Approval Number); BONE0001 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No