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Janet McLaren Gillian Lieberman, MD January 2002 An Introduction to PET Imaging in Oncology Janet McLaren, Harvard Medical School Year III Gillian Lieberman, MD Janet McLaren Gillian Lieberman, MD Basics of PET • Principle of “Physiologic Imaging:” – Allows in vivo visualization of structures by their ability to concentrate specific labeled molecules – Most commonly used compound: fluorodeoxyglucose (FDG) • Past use had been limited due to cost of dedicated PET scanners and the difficulty in obtaining isotopes • Recent advances have made PET more feasible: – Modification of dual head gamma camera SPECT systems – Increase in availability of isotopes 2 Janet McLaren Gillian Lieberman, MD FDG: The Compound CH2OH O OH HO OH [18F] FDG • 2-deoxy-2-(18F)fluoro-D-glucose • 18F: positron-emitting isotope of fluorine • Metabolically active cells utilize more glucose than other tissues and therefore uptake more FDG • FDG is phosphorylated by hexokinase upon entry into the cell but cannot undergo further glycolytic reactions • Dephosphorylation of the compound is slow, limiting transport out of the cell 3 Janet McLaren Gillian Lieberman, MD FDG: The Isotope CH2OH O OH HO OH [18F] FDG • 18F: emits positrons as it decays • Positrons travel until they collide with an electron • This collision produces two electromagnetic pulses of 511 keV that are detected by the PET detectors • Signal can be quantified: SUV (standardized uptake value) (+) – SUV > 2.5 generally used to indicate “increased uptake” 4 Janet McLaren Gillian Lieberman, MD Applications • Oncology – Diagnosis: benign vs. malignant process – Staging – Post-therapy evaluation: response to tx or to identify recurrence PET is approved for imaging of lung, lymphoma, colon and melanoma cancers • Assessment of Cardiac Viability – Used to evaluate myocardial perfusion and viability • CNS – Functional analysis 5 Janet McLaren Gillian Lieberman, MD Oncologic Imaging • FDG identifies hypermetabolic cells: – Malignancy – Infection – Inflammation • FDG false (-)s, specific to malignancy: – Small tumor size – Relatively low tumor metabolic activity (i.e. welldifferentiated tumors, including bronchoalveolar) – Hyperglycemia: dilutes uptake of FDG 6 Janet McLaren Gillian Lieberman, MD PET and the SPN • • • • 130,000 new Solitary Pulmonary Nodules (SPN)/year 40% of non-calcified SPN seen on CXR are benign A significant number of these remain indeterminate after CT Transthoracic FNA: high false (-) rate, diagnosis obtained in less than 50% of patients • PET: – Sensitivity and specificity of 95% and 81% for detecting malignancy PET Imaging is for patients who will have treatment planned according to PET results, i.e. thoracotomy or f/u 7 Janet McLaren Gillian Lieberman, MD PET and the DDx of a SPN DDx: • Benign Tumor • Round pneumonia • Malignant Tumor • A/V malformation SUV >2.5 Narrowed DDx: • Cancer • Cancer • Metastatic Tumor • Rheumatoid Nodule • Cancer • Granuloma • Granuloma/Rheumatoid From BrighamRad Teaching Cases: http://brighamrad.harvard.edu/Cases/bwh/hcache/147/full.html From Metro Region PET Center: SPN Case Study http://www.woodburnnm.com/study_spn.htm 8 Janet McLaren Gillian Lieberman, MD • Oncologic Applications of PET: – Diagnosis – Staging – Follow-up • Post-surgical • Response to chemo/RT Utility of PET in each of these areas varies among the different types of cancers From GE Medical Systems http://www.gemedicalsystems.com/index.html 9 Janet McLaren Gillian Lieberman, MD Patient #1: SPN Nodule • 84 year-old man with a solitary pulmonary nodule found on routine CXR. • Nodule was followed by CT for 2 years and found to be stable. • A few years later, PET became available for SPN evaluation. Courtesy of Dr. Vincent Chan, BIDMC 10 Janet McLaren Gillian Lieberman, MD Patient #1: SPN • A PET Scan showed the nodule to have increased activity • The nodule was biopsied and found to be an adenocarcinoma Courtesy of Dr. Vincent Chan, BIDMC 11 Janet McLaren Gillian Lieberman, MD Patient #1: SPN Lung CA • Diagnosis – PET can diagnose lesions deemed indeterminate by CT and thus is invaluable in the work-up of a SPN • Staging – In patients with known NSCLC, PET provides significant staging and prognostic information • CT vs PET in assessment of nodal status • 1999 Study: PET changed tx in 37% of cases Appropriate use of PET in the work-up of a SPN will prevent unnecessary operations and may prove to be cost effective 12 Janet McLaren Gillian Lieberman, MD Patient #2: Breast Cancer • 58 year-old woman presented with a breast mass after many years without clinical care • This mammogram was obtained • Diagnosed with inflammatory breast cancer • The patient was referred to Nuclear Medicine for staging From Southern Illinois University School of Medicine (www.siumed.edu/biomed/098-005.htm) 13 Janet McLaren Gillian Lieberman, MD Patient #2: Breast Cancer • PET Scan findings: – Primary Left Breast Mass – Mets to the Left Axilla LNs – Met to the Liver movie Courtesy of Dr. Vincent Chan, BIDMC 14 Janet McLaren Gillian Lieberman, MD Patient #2: Breast Cancer • Diagnosis – Most breast cancer is detected by mammo or PE – PET can be used for equivocal lesions to avoid biopsy, or in patients with prior surgery or implants • Staging – Sentinel Node Biopsy remains the preferred method of detecting axillary node metastsis – PET plays a useful role in identifying distant metastases • Shown superior to bone scan in detecting osteolytic lesions • Follow-Up – Limited data show PET can be used to monitor response to chemo as early as 8 days into treatment 15 Janet McLaren Gillian Lieberman, MD Patient #3: Melanoma • 35 year-old man presented with a lesion on his back • On excision, the lesion was found to be invasive melanoma • Patient was referred to Nuclear Medicine for staging 16 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #3: Melanoma PET Scan showed high activity in the left axilla and in a small area of the upper mediastinum 17 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #3: Melanoma • The increased activity in the upper mediastinum was thought to be artifact • The patient was treated with surgical excision of the left axillary lymph nodes 18 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Normal brain uptake Patient #3: Melanoma Healing tissue • 6 months later the patient returned for follow-up • The follow-up PET Scan revealed growth of the upper mediastinal mass • The mass was excised and confirmed to be metastatic melanoma 19 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #3: Melanoma • Staging – Sentinel Node Biopsy remains the preferred method of determining regional lymphatic spread – PET is preferred and superior to CT and MRI for identifying distant metastatic lesions – Data: sensitivity and specificity of 94% and 83% for PET vs. 55% and 84% for CT PET is very useful in identification and staging of cancers that metastasize widely or in an unpredictable manner (e.g. melanoma, lymphoma, head and neck cancer ) 20 Janet McLaren Gillian Lieberman, MD Patient #4 • 78 year old female • S/p colectomy and partial hepatectomy for metastatic colon CA seven years prior • Rising CEA (10.0) Courtesy of Dr. Vincent Chan, BIDMC 21 Janet McLaren Gillian Lieberman, MD Patient #4: Colon CA Abdominal CT findings: Courtesy of Dr. Vincent Chan, BIDMC Seroma Rib end? 22 Janet McLaren Gillian Lieberman, MD Patient #4: Colon CA ? Rib end 23 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #4: Colon CA As Abdominal CT was inconclusive, the patient was referred to Nuclear Medicine for a PET Scan. 24 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #4: Colon CA PET Scan revealed uptake in the chest wall scar, consistent with seeding during removal of the liver metastasis and recurrence. 25 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #4: Colon CA PET Imaging of the pelvis revealed another site of recurrence at the removal site of the primary tumor. 26 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #4: Colon CA PET Imaging of the pelvis revealed another site of recurrence at the removal site of the primary tumor. 27 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #4: Colon CA • Diagnosis – Highly sensitive in identifying colonic lesions, but not very specific (100% and 43%) • Staging – Good for evaluating distant metastases; lymph nodes to close to primary tumor to see • Follow-up – CTs are difficult to evaluate in the post-op patient due to fibrosis and distorted anatomy – PET Scans are very useful in follow-up patients by identifying recurrent lesions in areas of scar tissue 28 Janet McLaren Gillian Lieberman, MD Keeping a DDx FDG identifies hypermetabolic cells Malignancy Infection Inflammation 29 Janet McLaren Gillian Lieberman, MD Lets review some positive PET scans that were NOT due to malignancy 30 Janet McLaren Gillian Lieberman, MD Patient #5 • 60 year old female • Referred for evaluation of a SPN in the right upper lobe RV LV ? Cross-section at T9 level 31 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #5 32 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #5 Hiatal Hernia Increased metabolic activity from inflammation 33 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Patient #6 • 41 year-old man • History of hepatocellular carcinoma • Chevron Incision Increased metabolic activity of healing tissue 34 Courtesy of Dr. Vincent Chan, BIDMC Janet McLaren Gillian Lieberman, MD Summary • PET is one of the most exciting fields in modern Nuclear Medicine • When used in correlation with anatomic imaging, PET can provide important physiologic information • The modality has become very useful in the diagnosis, staging, and follow-up of oncologic disease • Great opportunity for advances in PET imaging: – isotopes tailored for specific cancers – new detectors to improve image resolution 35 Janet McLaren Gillian Lieberman, MD Acknowledgements • Vincent Chan, MD and the Nuclear Medicine Department of the BIDMC • Gillian Lieberman, MD • Pamela Lepkowski • Larry Barbaras and Cara Lyn D’amour, our Webmasters 36 Janet McLaren Gillian Lieberman, MD References • • • • • • Bar-Shalom R, Valdivia AY, Blaufox MD. PET Imaging in Oncology. Sem Nuc Med 2000; 30(3): 150-185. Bax JJ, Patton JA, Poldermans D, Elhendy A, and Sandler MP. 18Fluorodeoxyglucose imaging with Positron Emission Tomography and Single Photon Emission Computed Tomography: Cardiac Applications. Sem Nuc Med 2000; 30(4):281-298. Delbeke D, Martin WH. Positron Emission Tomography Imaging in Oncology. Rad Clin NA 2001 Sept; 39(5): 883-917. Saunders CA, Dussek JE, O'Doherty MJ, Maisey MN. Evaluation of fluorine-18fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer. Annals of Thoracic Surgery1999 Mar; 67(3):790-7. Schwartz B and Udelson JE. Assessment of myocardial viability by nuclear imaging in coronary heart disease. Up-to-Date version 9.3, 2001. Stark P. Computed Tomography and Positron Emission Tomographic scanning of pulmonary nodules. Up-to-Date version 9.3, 2001. 37