Integrated FDG-PET and PET/CT: Clinical Applications
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Integrated FDG-PET and PET/CT: Clinical Applications and Impact on Patient Care Dominique Delbeke, MD, PhD Vanderbilt University Medical Center Nashville, TN Quanta, Curitiba, Brazil Mayo 26th, 2009 Positrons Emitters Produced in a cyclotron Fluorine-18 (T1/2 = 110 min) Nitrogen-13 (T1/2 = 10 min) Carbon-11 (T1/2 = 20 min) Oxygen-15 (T1/2 = 2 min) Copper-64 (T1/2 – 12 h) Iodine-124 (T1/2 = 4 days) Produced by generator Rubidium-82 (T1/2 = 78 sec) Gallium-68 (T1/2 = 68 min) Copper-62 (T1/2 = 10 min) RDS-111 PET Cyclotron (CTI, Knoxville, TN) Assessment of Tumor Biology with PET PET assesses physiology and biochemistry rather than anatomy Therefore PET provides the potential for earlier, more sensitive detection of disease PET Tracers of Perfusion Tracers of Perfusion 15O-water (cyclotron, T1/2 = 2 min) 13N-ammonia (cyclotron, T1/2 = 10 min) 82Rubidium (generator expensive! T1/2 = 78 sec) Assessment of Tumor Biology with PET Perfusion Metabolism Glucose metabolism: 18F-fluorodeoxyglucose = FDG Bone metabolism: 18F-fluoride Membrane lipid synthesis:11C-acetate (i.e. HCC), 18F-choline Amino acid transport and metabolism: 11C-methionine , 18Ftyrosine Cellular proliferation: 18F-fluorothymidine (FLT) Receptor expression: Estrogen receptors 18F-fuoroestradiol e.g. Breast cancer Dopamine receptors: 18F-fluoro-DOPA e.g. Prostate cancer, neuroendocrine tumors Benzodiazepine receptors: 18F-flumazenil e.g. Epilepsy Somatostatin receptors: 68Ga-DOTA TOC and NOC More Promising PET Tracers Cellular oxygenation-hypoxia: 18F-MISO, 64CuATSM Hypoxia increases resistance to XRT Hypoxia leads to phenotypic heterogeneity Drug binding-sensitivity Gene expression/Gene therapy Cell death/apoptosis: Annexin Angiogenesis:18F-galacto-RGD targeting avB3 integrin expression, a critical angiogenic modulator Clinical Applications for FDG PET and PET/CT PET with FDG = imaging modality allowing direct evaluation of the cellular glucose metabolism Neurology Brain Tumors HIV positive patients with neurological symptoms Epilepsy Neuropsychiatric disorders (dementias) Cerebrovascular disease Cardiology Myocardial perfusion: 13N-ammonia, 82Rb Myocardial viability: 18F-FDG Oncology Glycogen Glycogen Glucose Glucose Hexokinase Hexokinase Glucose-6-P Glucose Glucose-6-P Glucose Cell Cell membrane membrane and and capillary capillary H Pentose-P H22O O ++ CO CO22 Pentose-P Hexokinase Hexokinase FDG FDG FDG FDG FDG-6-P FDG-6-P Normal Distribution of FDG Brain: high uptake in the gray matter Myocardium: variable uptake Lungs: low uptake Mediastinum: low uptake Liver: low uptake GI tract: variable activity (esophagus, stomach, colon) Urinary tract: excretes FDG Muscular system: low uptake at rest Cook GJR, et al: Semin Nucl Med 1996;26:308-314 Clinical Applications for PET in Oncology Most malignant tumors: Increased number of glucose transporter proteins Increased glycolytic enzyme levels Æ Increased FDG uptake compared to normal cells FDG PET became an established imaging modality for: Diagnosing malignancies Staging and restaging malignancies Monitor therapy Assess recurrence Surveillance Screening Positron Decay Instrumentation for PET Imaging Dedicated PET tomographs Gamma Camera Based PET = Hybrid PET Dedicated PET tomographs with BGO detectors (most commo GE Advance Anatomical & Molecular Imaging Are Complimentary Limitations of CT: Size criteria for lymph nodes involvement Differentiation of unopacified bowel versus lesion Evaluation of tumors after therapy Equivocal lesions Limitations of FDG PET: Limited resolution Accurate localization of the abnormalities Physiological variations of FDG distribution Optimal interpretation: In conjunction with each other Æ Integrated PET/CT is optimal and became available in year 2000 Integrated PET/CT Imaging Systems CTI Reveal GE Discovery LS and ST Philips Gemini (GSO) CPS Biograph (BGO) (LYSO, time of flight) (BGO and LSO) Diagnostic CT Scanner Multislice (2 – 4 slices/rotation originally, now 8,16, …., 64) 0.5 seconds/rotation, helical Scan – 17 seconds/meter Properties of common scintillation crystals Crystal Effect NaI (Tl) BGO GSO Density Stopping power 3.67 7.13 6.7 7.40 51 75 59 65 Atomic # LSO Light output Energy resol Spatial resol Scatter 100 15 25 75 Decay time Dead time Count rate 230 300 30-60 3545 Yes No No No Hygroscopic Integrated PET/CT Imaging System Benefit of the combined technique: 1) Attenuation correction with CT 2) Anatomical localization Discovery LS orSTE (GE Healthcare) PET CT Attenuation Correction Anatomical localization Integrated PET-CT Scanners Spectrum of equipment available: The quality of the PET images depends on the PET system and protocol. Resolution of the integrated CT images depends on the CT system and the protocol. Issues: Optimal CT protocols (IV contrast, breathing pattern, etc..) Patient positioning Operation of PET-CT systems: RT versus CNMT Interpretation and reports: radiologist versus nuclear medicine physicians Cost and billing Correction for Attenuation Artifacts Attenuation effects are more significant in coincidence imaging than SPECT because both annihilation photons must pass through the region without interaction. Methods: Calculated attenuation correction: e.g. Brain Measured attenuation correction using attenuation maps (transmission scan) obtained with various transmission sources: Typically sources of Ge-68 X-ray source Transmission Ge-68 rod sources on the GE Advance PET Scanner Advantages of Correction for Attenuation Improvement of the anatomic delineation Lesions can be localized more accurately Necessary for semiquantitative evaluation with SUV May be helpful for specific clinical situation e.g. indeterminate pulmonary nodules e.g. monitoring therapy no AC AC No AC Correction for Attenuation Artifacts The quality of the images with attenuation depends of the accuracy of registration of the emission and transmission scan. Inaccurate repositioning of the patient between scans can be avoided by performing simultaneous or sequential transmission/emission scans without moving the patient from the imaging table. Motion of the patient is a problem. Optimal correction for attenuation can be obtained using integrated PET/CT systems. An 81-year-old female presented with a left lung mass FDG PET without AC FDG PET with AC Diagnosis: The apparent decreased uptake in the R MCA territory is due to patient’s motion between emission and transmission scan Respiratory motion -Æ misregistration With AC Without AC Patient shifted to the right for PET acquisition Æ misregistration (physiologic muscular uptake projects over the left femoral head CT for Attenuation Maps High quality maps because of high photon flux Low current (10 mA) provides satisfactory attenuation maps. Short duration < 1 minute from base of the skull to mid-thigh with multidetector CT. Also provide anatomical maps for lesion localization Current of ~80 mA is a compromise for limited radiation dose Whole body dose equivalent ~ 700 mrem (7.0 mSv) Whole body dose equivalent for FDG (10 mCi) ~700 mrem Whole body dose equivalent for whole body PET-CT: ~ 4.8 years background radiation in US Technical Protocol for whole body PET/CT (GE Discovery STE at VUMC) Transmission CT 80 mA (fixed or adjust to patient’s weight) 130-140 kVp 40-90 msec 5 mm slices Pitch 3/1 No IV contrast Breath-hold at Tidal volume or normal breathing Emission PET 2D: 4 min/bed position 3D: 2min/bed Regional diagnostic CT with IV and oral contrast if indicated Beyer T, et al. J Nucl Med 2004;45 (Suppl): 25S Artifacts on CT-attenuated PET images Inaccurate co-registration due to: Random motion (but less likely with short transmission scan) Respiratory motion Curvilinear cold artifacts along diaphragm Inaccurate localization of lesion in the region of diaphragm (dome of liver versus lung bases) in 2% of patients Goerres GW et al. Radiology 2003;226:906-910. Osman MM et al. Eur J Nucl Med 2003;30:603-606. Osman MM et al. J Nucl Med 2003;44:240-243. 65 year-old with lung cancer s/p XRT to mediastinum 1 week earlier Radiation esophagitis Curvilinear photopenia along diaphragm due to motion of diaphragm Artifacts on CT-attenuated PET images Hot spots due to over-correction related to: IV contrast Focal accumulation of oral contrast Metallic implants (dental, hardware…) Overestimation of SUV values by up to 10% compared to Ge-68 based attenuation correction. Antoch G et al.J Nucl Med 2002;43:1339-1342. Cohade C et al. J Nucl Med 2003;44:412-416. Goerres GW et al. Eur J Nucl Med Molec Imag 2002;29:367-370. Nakamoto Y et al. J Nucl Med 2002;43:1137-1143. Antoch G et al. J Nucl Med 2004: 45 (Suppl): 56S. SNM Procedure Guideline SNM Guideline J Nucl Med 2006; 47 (May): 885 SNM Procedure Guidelines for FDG PET/CT Purpose Background Information and Definitions Procedure Patient Preparation Information Pertinent to Performing the Procedure (focused history) Radiopharmaceutical Image Acquisition Intervention Processing Interpretation Criteria Reporting Quality Control Sources of Error Qualification of Personnel SNM Guideline J Nucl Med 2006;47:1227 Sources of False +/- Interpretations F+: Physiologic FDG uptake Lymphoid tissue Brown adipose tissue Glandular tissue Muscular system GI tract GU tract F+: Inflammation Therapy-related Therapy-related: Ostomies, drainage tubes, stents (percutaneous more common), radiation therapy , chemotherapy Trauma Infection Abscesses, Acute cholecystitis, Acute cholangitis, Acute pancreatitis (chronic pancreatitis but uncommon), Inflammatory bowel disease, Diverticulitis Granulomatous disease: TB, fungi Sources of False +/- Interpretations False negative include: Small lesions (<5-10 mm, i.e. ampullary carcinomas, miliary carcinomatosis) Low cellular density Tumors of the infiltrating type (cholangiocarcinomas) Tumors with large mucinous components Tumor necrosis Some low grade tumors: Lymphoma, sarcoma,… Low sensitivity: ~ 50-80% GU: Prostate, Renal cell GYN: Ovarian (mucinous, miliary spread) Hepatocellular Differentiated neuroendocrine Bronchioalveolar Hyperglycemia and/or insulin less than 3 H prior to FDG NOPR: National Oncologic PET Registry A Nationwide (US) Collaborative Program 2006-2008 Nationwide prospective registry Goal: evaluate the impact of PET on physicians plans of patient management Providers are required to submit data from pre- PET and post-PET physician questionnaires to NOPR as a condition for reimbursement NOPR: National Oncologic PET Registry A Nationwide (US) Collaborative Program Sponsored by Advisor Managed by Endorsed by Chair, Bruce Hillner, MD, Virginia Commonwealth University Co-chair, Barry A. Siegel, MD, Washington University R. Edward Coleman, MD, Duke University Anthony Shields, MD, PhD Wayne State University Statistician: Dawei Liu, PhD, Brown University Epidemiologist: Ilana Gareen, PhD, Brown University NOPR: Cohort Profile • First year of NOPR (5/8/06 to 5/7/07) • 22,975 “consented” cases from 1,519 facilities • Technology profile – 84% PET/CT – 71% non-hospital – 76% fixed sites – Indications – Diagnosis 24% – Initial staging 28% – Restaging 24% – Recurrence 24% Hillner et al., J Clin Oncol 2008;26 (13):2155-61. NOPR: National Oncologic PET Registry PET Changed Intended Management in 36.5% of Cases Clinical Indication for PET Study (%) Pre-Pet Plan Post-PET Plan Treat Dx Staging Restaging Recurrence All n=5,616 n=6,464 n=5,607 n=5,388 n=22,975 Same 16.0 46.5 15.8 20.4 25.5 Non-Treat Same 52.9 14.0 48.0 40.7 37.9 Non-Treat Treat 23.2 31.6 28.6 29.2 28.3 Treat Non-Treat 7.9 7.9 7.5 9.7 8.2 31.1 39.5 36.1 39.0 36.5 Patients with change post-PET (%) Hillner et al., J Clin Oncol 2008;26 (13):2155-61. NOPR: National Oncologic PET Registry PET Impact on Management by Cancer type: Overall 38% of Cases Impact of PET on intended management in the top 10 cancers in the NOPR Cancer No. of scans % imaging% change in intended treatment adjusted impact Prostate 5,309 35.1 15.0 Ovary 4,509 41.4 16.2 Bladder 3,578 37.9 15.4 Pancreas 3,314 39.0 14.8 Stomach 3,025 36.9 14.5 Small-cell lung 2,983 41.2 13.1 Kidney 2,877 35.8 16.0 Uterus 2,869 36.5 15.1 Myeloma 1,784 48.7 11.5 Connective Tissue 1,350 36.4 13.6 Hillner B et al. J Nucl Med 2008;49 (12):1928-35 NOPR: National Oncologic PET Registry PET Changed Intended Management during Cancer Treatment 8,240 patients who had 10,497 treatment monitoring PET scans at 946 centers Chemotherapy alone 82% Radiation therapy alone 6% Combination 12% 37% of patients had ovarian, pancreatic or lung cancers 54% of scans had pre-PET summary stage was metastatic disease Hillner B et al. Cancer 2009;115 (2):410-18 NOPR: National Oncologic PET Registry PET Changed Intended Management during Cancer Treatment 8,240 patients who had 10,497 treatment monitoring PET scans at 946 centers If PET was not available, intended management : Other imaging 53% Ongoing treatment 41% Biopsy or watching 6% Post- PET intended management: Switching to another therapy: 26-28% of scans Adjusting of dose or duration of therapy: 16-19% of scans PET enabled 91% of patients to avoid future tests Hillner B et al. Cancer 2009;115 (2):410-18 Summary Table of Medicare Coverage Policy (US) for FDG PET/CT as of April 2009 Cancer Type Initial Treatment Strategy Evaluation Subsequent Treatment Strategy Evaluation Breast Covered 1 Covered Cervix Covered 2/ CED Covered Colorectal Covered Covered Esophagus Covered Covered Head Neck Covered Covered Lymphoma Covered Covered Melanoma Covered 3 Covered Myeloma Covered Covered NSCLC Covered Covered Ovary Covered Covered Prostate NC CED Thyroid Covered Covered 4/CED All other solid tumors Covered CED a T Q FDG PET and PET/CT are included in the practice guidelines for 21 cancers Anal Bone sarc. CNS (lymph) Cervix Colon Esophagus Gastric Head/Neck Hodgkin Lung The utility of FDG PET is recognized by 21 member institutions of the NCCN Melanoma Myeloma NHL Merkel cell Occult 1’ Ovarian Rectum Small lung Sarcoma Testicular Thyroid NCCN: Task Force meeting Nov 2006 Breast cancer Colorectal cancer Lung cancer Lymphoma Podoloff DA et al. J Natl Compr Canc Netw 2007;May;5 Suppl 1: S1-S22. NCCN: Task Force meeting Nov 2008 NOPR update Genitourinary cancers Gynecological cancers Pancreatic cancer Hepatobiliary cancers Sarcoma Thyroid cancer Brain cancer Small cell lung cancer Myeloma Gastric and esophageal cancers Podoloff DA et al. J Natl Compr Canc Netw 2009; 7 Suppl 2:S1-S24. Thank you! Grand Bahama 2004
