18F-Sodium Fluoride (NaF) PET/CT Bone Scan Indications

Introduction
        
Effective February 7, 2011, PET/CT studies utilizing the radiopharmaceutical, 18F-Sodium Fluoride (NaF) are covered for the detection and evaluation of bone metastases for Medicare beneficiaries through the Coverage with Evidence Development/ National Oncologic PET Registry program (NOPR).

18F-Sodium Fluoride (NaF) PET/CT is an important tool for detecting and evaluating metastatic bone cancer. These bone studies are particularly useful, since some of the most prevalent cancers are commonly associated with metastatic bone disease, such as breast and prostate cancer, as well as carcinoma of the thyroid, kidney, and lung. This expansion of coverage for 18F-Sodium Fluoride (NaF) studies provides a superior clinical alternative for bone scanning, with significant advantages over “conventional” 99mTc-MDP bone scans, including higher sensitivity and specificity, shorter uptake and scan times, and radiation doses comparable to 99mTc-MDP studies.

Background to 18F-Sodium Fluoride (NaF)
18F-Sodium Fluoride (NaF) has been an approved radiopharmaceutical for imaging areas of altered osteogenic activity since its initial FDA approval in 1972. However, for a number of decades 18F-Sodium Fluoride (NaF) was not widely used, due in large part to the widespread use of conventional bone scintigraphy utilizing 99mTc phosphate and phosphonate radiopharmaceuticals. Recent years have witnessed a resurgence in interest in 18F-Sodium Fluoride (NaF) as a bone imaging agent, due to evidence indicating the superior sensitivity and specificity of 18F-Sodium Fluoride (NaF) PET when compared with conventional 99mTc-MDP bone scans. The recent worldwide shortages of 99mTc-MDP and the ready availability of 18F-Sodium Fluoride (NaF) have increased interest in 18F-Sodium Fluoride (NaF) PET.

18F-Sodium Fluoride (NaF) has a number of desirable characteristics as a bone-imaging agent, including:

• Bone uptake is two times higher and blood clearance is much faster than 99mTcMDP, offering superior bone to background ratios and high contrast images within 45-60 minutes after injection.

• Improved sensitivity compared to traditional nuclear medicine SPECT or planar bone imaging, due to 18F-Sodium Fluoride (NaF) ability to demonstrate variation in bone metabolism, combined with the PET/CT scanner’s high resolution, tomographic images. Bone metastases are seen indirectly, with uptake depending on skeletal reaction to tumor.

• Little residual retention in soft tissues and the renal parenchyma.

• Deposition favors sites of high bone turnover and remodeling.

• Comparable radiation dose to conventional 99mTc-MDP bone scan.

Approved Clinical Indications for 18F-Sodium Fluoride (NaF) PET/CT Studies
On February 7, 2011 CMS approved coverage of 18F-Sodium Fluoride (NaF) PET/CT bone scans through the NOPR for Medicare beneficiaries with known or suspected cancer. Coverage is provided for the following cancer indications:

Clinical areas in which 18F-Sodium Fluoride (NaF) PET/CT studies are valuable include: (1) Evaluation of metastatic bone disease; (2) Initial staging for patients at risk for bone metastases; (3) Situations in which exclusion of bone disease is required prior to initiation of potentially curative therapy; (4) Following patients with bone dominant metastases, to evaluate effectiveness of systemic therapy, and to exclude new metastases at critical anatomic sites.

Advantages of 18F-Sodium Fluoride (NaF) PET/CT studies over conventional 99mTc-MDP studies

In 2009, the Division of Cancer Treatment and Detection of the National Institutes of Health (NIH) conducted a review concerning 18F-Sodium Fluoride (NaF) PET imaging and its utility for assessing cancer metastases to bone. A Report Summary noted that,

“Diagnostic imaging has played a major role in the evaluation of patients with bone metastases, and this application is the focus of the majority of the recent published literature on use of 18F-fluoride PET. For detection of bone metastases in cancer patients, doses typically ranged from 8-12 mCi. In thi8s dose range, excellent image quality with higher spatial resolution than BS (conventional bone scans) is obtained. There is evidence that 18F-fluoride PET is more sensitive and selective than conventional BS for diagnosis and detection of bone metastases…Use of low dose CT in conjunction with 18F-fluoride PET improves sensitivity and specificity, and improves the ability to distinguish benign from malignant lesions. Because of these advantages, and advancements in cost-effeciveness, it has been suggested that 18F-fluoride PET will replace conventional bone scan for detection of bone metastases within several years”.

18F-Sodium Fluoride (NaF) PET/CT studies have a number of advantages over conventional 99mTc-MDP studies, including:

• Higher accuracy in detecting both osteolytic and osteoblastic metastases
• Greater differentiation of benign versus malignant lesions
• Increased sensitivity over 99mTc scans
• Increased specificity over 99mTc scans
• Increased spatial and contrast resolution
• Fusion with anatomic information gained from integrated CT
• 3-axis and whole body viewing similar to FDG PET studies
• 18F-Sodium Fluoride (NaF) radiopharmaceutical readily available for use. Supply not constrained, as is the case with 99mTc

From an operational standpoint, the faster completion of whole body scanning with 18F-Sodium Fluoride (NaF) PET/CT is significant, providing greater comfort and convenience for the patient. While the waiting time between radiopharmaceutical injection and the actual scan is 45-60 minutes for 18F-Sodium Fluoride (NaF) PET/CT, the waiting time for a conventional bone scan is some 3 hours. The actual scanning time for the 18F-Sodium Fluoride (NaF) PET/CT is generally 15-20 minutes, as compared with 45-60 minutes for the conventional bone scan.

Frederick D. Grant et al have published an article in the January 2008 Journal of Nuclear Medicine, “Skeletal PET with 18F-Flouride: Applying New Technology to an Old Tracer” that considers the advantages and clinical utility of 18F-Sodium Fluoride (NaF) PET/CT studies. For a pdf of this article, click here.

Other widely cited articles on the advantages of 18F-Sodium Fluoride PET/CT bone studies over conventional 99mTc-MDP studies include:

• Schirrmeister, H., et al “Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET” Journal of Nuclear Medicine 1999; 40:1623-1629.

• Schirrmeister, H., et al “Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography”. Journal of Clinical Oncology. 1999; 17: 2381-2389.

• Schirrmeister, H., et al “Prospective evaluation of the clinical value of planar bone scans, SPECT, and 18F-labeled NaF PET in newly diagnosed lung cancer”. Journal of Nuclear Medicine. 2001; 42: 1800-1804.

Case studies illustrating clinical applications of 18F-Sodium Fluoride (NaF) PET/CT may be found by clicking this link to our Case Studies pages.