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PET F18 Bone Imaging

This tutorial will assist the leaner in understanding the fundamentals of PET F18 Bone Imaging. The course will take you through the history bone scintigraphy, the differences between SPECT and PET radionuclides, indications for bone imaging, current tools used to evaluate bone metastasis, FDG’s role in bone imaging, reasons for using Sodium Fluoride, a typical protocol and provide an overview of some case studies.

Welcome to PET Bone Scan Imaging with *Sodium Fluoride F18 web based training. This course will review the advantages of Sodium Fluoride Bone PET as an alternative to Technetium 99m polyphophonate planar or SPECT Nuclear Bone imaging. *Important safety information is available at the end of this course.  Please see accompanying full prescribing information.   Image courtesy of SIEMENS Healthcare By the end of the tutorial, you will have learned: History of functional bone imaging Differences in SPECT and PET Radionuclides Oncologic applications for bone imaging Facts about bone metastatic diseases Tools  for bone metastatic evaluation Advantages of using *18F Sodium Fluoride (18F NaF) Typical Protocol and Case Studies *Important safety information is available at the end of this course.  Please see accompanying full prescribing information. 1950-1960 2000-present 1960 1970 1972 1980 1990 Rectilinear Scanner Introduction of *F18 NaF Planar Anger Gamma Camera FDA Approves 18F NaF for Oestrogenic Changes PET Hybrid Systems SPECT *Important safety information is available at the end of this course.  Please see accompanying full prescribing information. Rectilinear Scanner 1950 to 1960 1951 Cassen Calcium analogues 85 Strontium : 514 KeV Half-life 65 days Only for metastatic disease Therapeutic dose 1960 introduction of *F18 NaF : 511KeV Positron Half-life 110min Problem: No cyclotron network *Important safety information is available at the end of this course.  Please see accompanying full prescribing information. Planar Anger Gamma Camera 1960 to Present 1958 Hal Anger invented Gamma Camera 1958 Brookhaven Lab invented 99Mo/99mTc Generator 1971 Subramanian & McAfee invented Phosphate Compounds Planar Bone Scans are still Standard: 99mTc MDP/HDP SPECT Gamma Camera 1980 to Present Circular and Non-Circular Acquisition Increased Sensitivity & Specificity Increased Acquisition Time Used for indeterminate Vertebral Lesions & Back Pain FDA Approved *18F NaF to Define Areas of Altered Osteogenic Activity 1972 No Cyclotron Network Poor image quality with Gamma Camera Easier access to 99mTc Compounds Better image quality *Important safety information is available at the end of this course. Please see accompanying full prescribing information. Food and Drug Administration Modernization Act 1997 FDAMA 1997 *18F Sodium Fluoride *Fluorodeoxyglucose F18 (FDG) Ammonia  N13  (NH3) Safe and Effective for Use *Important safety information is available at the end of this course. Please see accompanying full prescribing information. PET Standalone Systems 1990 - Present Systems: Full Ring Partial Ring Coincidence Gamma Cameras Useful for imaging *18F labeled radiopharmaceuticals *Important safety information is available at the end of this course. Please see accompanying full prescribing information. Hybrid Imaging   2000- Present PET-CT SPECT-CT MR-PET (no reimbursement yet) Indications and Applications for Use of *18F-NaF Metastatic Disease *Important safety information is available at the end of this course. Please see accompanying full prescribing information. Image courtesy of SIEMENS Healthcare Digital Image Processing Computer Correction & MCA Hardware Gamma Camera Head Collimator Position Data Energy Data Gamma Rays SPECT Tracer is injected Single gamma rays emitted Isotopes have specific energy Random direction Collimator Gamma Camera Digital Imaging Processor Tracer Detector Detector 511 keV 511 keV ß+ ß- ~1-3mm PET Tracer is injected Positrons collide with electrons Annihilation Two 511 KeV energy gamma rays at ~180 degrees Detection by opposing detectors Energy window Coincidence time window Approved Indication for *18F-NaF Indications in the Package Insert: *Sodium Fluoride F18 Injection is a radioactive diagnostic agent for positron emission tomography (PET) indicated for imaging of bone to define areas of altered osteogenic activity.   *Important safety information is available at the end of this course. Please see accompanying full prescribing information. Oncologic Applications for Bone Imaging Primary Bone Disease Metastatic Bone Disease Prior to Therapy Response to Therapy Image courtesy of SIEMENS Healthcare Evaluation Results of Bone Imaging Initial staging of patients at risk for bone metastases prior to therapy Image courtesy of SIEMENS Healthcare Following patients with bone metastases for effectiveness of systematic therapy Excluding new metastases located at critical anatomic areas   Axial skeleton (blue) Appendicular skeleton (pink) Cancer spreads Passive transport Extend from soft tissue to bone Intramedullary Lesions 90% of Bone Metastases Active Red Marrow Axial Skeleton of Adult (blue) Lesion grown in marrow Normal Bone Osteoclastic- resorptive Osteoblastic - productive Metastatic Lesions Lytic – marrow   Sclerotic blastic Mixed – lytic & sclerotic Lytic Lesions Breast, Bladder, Kidney, Thyroid, Multiple Myeloma Sclerotic Lesions Prostate, Breast Sometimes Lung, Stomach, Cervical, Pancreas, Colon Many patients are asymptomatic Found incidentally through routine screenings ~280,000 adults living with metastatic bone disease in the US. Occur in up to 70% of advanced stage breast or prostate cancer patients**   15%-30% of other cancers   *Source: US National Library of Medicine and the National Institutes of Health. **Source: New England Journal of Medicine, Mechanisms of Bone Metastasis, US National Library of Medicine and the National Institutes of Health, 2012. Facts About Bone Metastatic Diseases: Breast Cancer Distant Metastases ~26%-50% bone vertebral Ribs Metastases Mixed Sclerotic ( blastic) and Lytic (marrow) - mixed Image courtesy of Seattle Nuclear Medicine, Seattle, WA Facts About Bone Metastatic Diseases: Breast Cancer Early Stage I & II 0.8%-2.6% Bone Scan (patients who are symptomatic) Advanced Stage III & IV 16.8%-40.5% Bone scan Source: US National Library of Medicine and the National Institutes of Health, 2012. Advanced stage: 70% will have bone mets PSA Test Gleason Score Clinical Staging Normal prostate Benign prostatic hypertrophy (BHP) Early Stage No routine bone scan, only if patient is symptomatic T1 and T2: PSA >20 Advanced Stage High risk of metastasis T3: PSA > 20, Gleason > 8 Bone scan recommended Imaging Systems Currently Used in Bone Evaluation X-RAY CT MRI NM & SPECT Hybrid Systems X-RAY Limited info on bone marrow involvement   30%-75% reduction in density   Tools for Metastatic Bone Evaluation: Computed Tomography Excellent anatomic resolution and soft tissue contrast Structure, form and size   No function Common Uses for CT Assess equivocal bone lesions Differentiate malignant & benignant Fracture Spinal cord compression Aids for Biopsy Detecting soft tissue mass Used in Radiation Therapy Advantages of MR Good spatial and contrast resolution Optimal to assess bone marrow Red and yellow marrow Early detection Sensitive Image courtesy of SIEMENS Healthcare Disadvantages of MR Differentiation After Therapy Suggested After CT and Bone Scanning Less Sensitive Than CT Difficult for Degenerative Disk Disease, Osteomyelitis,    Benign Compression Fracture Tools for Metastatic Bone Evaluation: Nuclear Medicine and SPECT Standard Since 1970 Part of Initial Staging Workup Tracers 99mTc-methylene diphosphonate (MDP) 99mTc-oxidronate (HDP) 99mTc Pyrophosphate (PYP) Image courtesy of SIEMENS Healthcare Advantages Widely Available Lesions seen 2-18 months earlier than in X-Ray* Whole-body for osteoblastic metastases Disadvantages Planar versus SPECT SPECT time constraint Osteolytic lesions cold on bone scan *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 Excellent Anatomic Structure and Tissue Contrast Function and Metabolism Time Constraint Not Acquired Simultaneously Anatomic Structure and Tissue Contrast Function and Metabolism 15 min Whole body Scan No Simultaneous Acquisition Anatomic Structure and Tissue Contrast Function and Metabolism Simultaneous Acquisition Time Constraint Radiopharmaceuticals For PET Bone Imaging and Metastasis Image courtesy of SIEMENS Healthcare Increased Glucose Metabolism** Sensitivity ~62% and Specificity ~100% Soft Tissue & Lytic Skeletal Disease Early Detection of Marrow Disease Normal Marrow – Low Intensity Uptake Lytic Lesions – High Uptake Blastic Lesions – Low Uptake   **For use in PET imaging for assessment of abnormal glucose metabolism in the evaluation of malignancy in patients with known or suspected abnormalities found with other testing modalities, or in patients with an existing diagnosis of cancer. *Important safety information is available at the end of this course. Please see accompanying full prescribing information. *Sodium Fluoride F18 (18F NaF): Superior Method for Detection of Bone Metastasis *Important safety information is available at the end of this course.  Please see accompanying full prescribing information.   18F NaF is a drug and is approved by FDA for use in the evaluation of altered osteogenic activity. Market place today: Expanded Cyclotron Network Increased number of PET•CT systems with “time available” Heightened  demand to grow procedure volume - post DRA Unit dose of sodium fluoride is widely available Better patient care: Ability to offer a more accurate technique Opportunity to further educate physicians on the value of PET Image courtesy of SIEMENS Healthcare Characteristics: *18F-NaF vs 99mTc-Phosphates Mechanism of Uptake Similar to 99mTc MDP Fluoride is incorporated into bone matrix and converts hydroxyapatite to fluoroapatite Absorbed into bone matrix at 2x the rate of the phosphonate mechanism resulting in 2x uptake compared to phosphate compounds 99mTc MDP *18F NaF Characteristics: *18F-NaF vs 99mTc-Phosphates Does not bind to protein unlike phosphate compounds Higher capillary permeability = Faster blood clearance Low background activity Deposited at sites with high bone turnover and favors axial skeleton Greater uptake in joints Image courtesy of SIEMENS Healthcare *Important safety information is available at the end of this course.  Please see accompanying full prescribing information. Images courtesy of SIEMENS Healthcare Studies and References PET *18F NaF vs. 99mTc MDP Planar Bone Scanning PET *18F NaF provides: Identification of 100% of known metastases Superior spatial resolution Twice as many benign and malignant skeletal lesion detections *18F-NaF PET = 97% accuracy vs. MDP Bone Scans = 80.5% Source: Schirrmeister, et al JNM 40: 1623-1629, 1999 85% (94/111) Mets Seen on *F18 NaF Correlated with Changes on CT Majority (16/17) of the remaining mets appeared normal on CT Confirmation of Mets via MRI and/or *FDG Bone Lesions, Increased Uptake, Normal CT Findings =  89% Malignancy Rate Sensitivity = 99% (lesion analysis), 100% (patient analysis), Specificity = 97% Source: Even-Sapir, MD, et al, JNM Vol 45, No 2, 2004 p 272-27 85% (94/111) Mets Seen on *F18 NaF Correlated with Changes on CT CT – Benign Abnormalities at Increased Tracer Uptake Location at 96% of Benign Lesions PET/CT Increased *F18 NaF Uptake, Normal CT Findings = High Malignancy Rate of 89% Source: Even-Sapir, MD, et al, JNM Vol 45, No 2, 2004 p 272-27 *Important safety information is available at the end of this course.  Please see accompanying full prescribing information. The aim of this study was to compare the detection of bone metastases by 99mTc-methylene diphosphonate (99mTc-MDP) planar bone scintigraphy (BS), SPECT, 18F-Fluoride PET, and 18F-Fluoride PET/CT in patients with high-risk prostate cancer.   __________________________________________________________________________________________ Study Head-to-Thigh Comparison: 99mTc MDP vs *18F NaF PET in 34 metastatic breast cancer patients with known or suspected bone mets   Results confirmed by MRI, CT, Radiographs In (11/17) patients, the extent of disease was underestimated 3 patients with normal MDP Planar had ACTUALLY metastases confirmed by *F18 NaF PET Results influenced clinical management in ~18% of patients Source: Schirrmeister, et al JCO 17:2381-2389 Aug 1999 *Important safety information is available at the end of this course. Please see accompanying full prescribing information. 99mTc MDP   *18F-NaF PET Findings Non Suspicious, Normal Mets to Spine and Pelvis Source: Schirrmeister, et al JCO 17:2381-2389 Aug 1999 Images courtesy of SIEMENS Healthcare Typical Protocol Example for PET Bone Imaging with *18F-NaF Patient Preparation: Well hydrated and void immediately before scanning No NPO Usual medications Usual precaution for pregnant patients Breastfeeding precautions as with *FDG Diuretics or bladder catheterization Typical Protocol Example for PET Bone Imaging with *18F-NaF Dosing Suggestions: Adult: 5-10 mCi Child: (5y)  0.07mCi/kg Patient Uptake Time Suggestions: 45 min to 60 min Extremities – longer uptake Typical Protocol Example for PET Bone Imaging with *18F-NaF Acquisition Parameter Suggestions - CT: Diagnostic CT recommended AC CT:  30 mAs or lower Acquisition Parameter Suggestions for PET: 2-5 mins/bed 3D acquisition recommended Matrix size: 168 or 256 Typical Protocol Example for PET Bone Imaging with *18F-NaF PET Reconstruction Imaging reconstruction parameters as used with FDG imaging Creating a MIP Image courtesy of SIEMENS Healthcare *Important safety information is available at the end of this course.  Please see accompanying full prescribing information. Case Studies *F18 FDG *F18 NaF 30 mCi 99mTc MDP 10 mCi FDG 10 mCi *18F NaF PET Images courtesy of Seattle Nuclear Medicine, Seattle, WA *Important safety information is available at the end of this course.  Please see accompanying full prescribing information. Images courtesy of Seattle Nuclear Medicine, Seattle, WA   F18 FDG 18F NaF Images courtesy of Seattle Nuclear Medicine, Seattle, WA PET Center of Excellence Case – 7/24/2009 Breast Cancer with Liver and Lung Metastasis 1/2009 6/2009 1/2009 6/2009 ← January 2009: Pelvis – Lytic Predominant Dx June 2009:   → Pelvis – Healing Flare Phenomenon   ← January 2009: Vertebrae – Mixed Lesion June 2009:   → Vertebrae – Sclerotic Predominant 1/2009 6/2009 Flare is greater than with MDP Response to tx requires CT or MRI co-registration to see bone changes Soft tissue lesions with calcifications-admixure of activity from both tracers Dual tracer imaging = all more encompassing imaging strategy PETNET link from Aunt Minnie  for more information on NaF PET bone imaging  https://www.smed.com/mi_am6/default.asp   Journal of Nuclear Medicine Technology, “An Introduction to Na18F Bone Scintigraphy: Basic Principles, Advanced Imaging Concepts, and Case Examples”, Vol. 35, No. 2, June 2007, pg. 64 - 76   Indications, Important Safety Information, Dosage Forms, and Strenths for *Fludeoxyglucose F18 Injection and *Sodium Fluoride F18 Injection   *Important safety information is available on the next few slides. Please see accompanying full prescribing information.   Indications & Usage Fludeoxyglucose F 18 injection (18F FDG) is indicated for positron emission tomography (PET) imaging in the following settings: Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.   Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.   Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.   *Please see accompanying full prescribing information.   Important Safety Information Radiation Risk: Radiation-emitting products, including Fludeoxyglucose F 18 Injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker.   Blood Glucose Abnormalities: In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to assure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration.   Adverse Reactions: Hypersensitivity reactions with pruritus, edema and rash have been reported; have emergency resuscitation equipment and personnel immediately available.   *Please see accompanying full prescribing information.   Indications & Usage Sodium fluoride F 18 injection is a radioactive diagnostic agent for positron emission tomography (PET) indicated for imaging bone to define areas of altered osteogenic activity.   *Please see accompanying full prescribing information.   Dosage Forms and Strengths Multiple-dose 30 mL and 50 mL glass vial containing 0.74 to 7.40 GBq/mL (20 to 200 mCi/mL) of Fludeoxyglucose F 18 injection and 4.5 mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a stabilizer (approximately 15 to 50 mL volume) for intravenous administration.   Fludeoxyglucose F 18 injection is manufactured by Siemens’ PETNET Solutions, 810 Innovation Drive, Knoxville, TN 39732   *Please see accompanying full prescribing information.   Important Safety Information Allergic Reactions As with any injectable drug, allergic reactions and anaphylaxis may occur. Emergency resuscitation equipment and personnel should be immediately available.   Cancer Risk Sodium fluoride F 18 injection may increase the risk of cancer. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and healthcare worker.   Adverse Reactions No adverse reactions have been reported based on a review of the published literature, publicly available reference sources and adverse drug reaction reporting systems. The completeness of the sources is not known.   *Please see accompanying full prescribing information.   Dosage Forms and Strengths Multiple-dose vial containing 370–7,400 MBq/mL (10–200 mCi/mL) at EOS reference time of no-carrier-added sodium fluoride F18 in aqueous 0.9% sodium chloride solution. Sodium Fluoride F 18 Injection is a clear, colorless, sterile, pyrogen-free and preservative-free solution for intravenous administration.   Sodium Fluoride injection is manufactured by Siemens’ PETNET Solutions, 810 Innovation Drive, Knoxville, TN 39732   *Please see accompanying full prescribing information.

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