: Dr. Sandor Demeter Nuclear Medicine HSC PET & Oncology


OVERVIEW :OVERVIEW Technology PET in USA PET in Canada Clinical Applications Oncology PET in Manitoba Questions


Physics : http://nucmed.rad.washington.edu/web/teaching/physics_intro/ Physics PET PHYSICS The Essence


18 F Range Max 2.4 mm, (FWHM 0.22 mm) :18 F Range Max 2.4 mm, (FWHM 0.22 mm)


Slide 5:[18O (p,n) 18F] Medical Cyclotron


Radiopharmaceuticalse.g. 18-O (p,n) 18-F : http://laxmi.nuc.ucla.edu:8000/lpp/shocked/lppshocked.html Radiopharmaceuticalse.g. 18-O (p,n) 18-F


Slide 7:Lawrence helped to usher in a new era in science with the invention of this small device, the cyclotron, in 1929. Now housed in the Smithsonian, it measures only five inches across. Largely because of this invention, scientists from across the country and around the world sought positions at U.C. Berkeley. Many others volunteered their services, and expertise to take part in research that, everyone involved knew, had unfathomable potential. It was ~ 5 inches in diameter! http://www.lbl.gov/LBL-PID/Berkeley-Lab-history.html Ernest Orlando Lawrence


Slide 8:Berkeley’s 184 inch cyclotron built 1942


Slide 9:Positron Emitters Half Lives Cyclotron 1 –10 min 10-20 min 1-6 hours 11C 13N 15O 82 Rb 18F 124I 64Cu > 10 hours t ½ Max min Range (mm) Rb 82 1.3 12.4 O 15 2 8.2 N 13 10 5.4 C 11 20 5.0 F 18 110 2.4


FDG Radiochemistry F-18 Max =0.64 MeV & 2.4 mm range, t ½ = 110 minutesF-18 to FDG in 27 minutes via nucleophilic substitution :Mankoff DA et al. Sem in Rad Onc 2001;11(1):16-27 FDG Radiochemistry F-18 Max =0.64 MeV & 2.4 mm range, t ½ = 110 minutesF-18 to FDG in 27 minutes via nucleophilic substitution [18O (p,n) 18F] hexokinase


Non FDG Oncology PET Tracers :Non FDG Oncology PET Tracers Estrogen receptor imaging (FES -fluorestradiol] Hypoxia imaging (18FMISO – misonidazole) Tumor proliferative index – [11C or 18F thymidine] Amino acid synthesis – [11C – methionine] Membrane synthesis –[11C choline] Perfusion/blood flow (H2O15) Chemotherapy delivery model – [18F fluoruracil] http://www.crump.ucla.edu/software/lpp/r


Slide 12:Biograph PET-CT Siemens Exact HR Plus and Exact


Advantages of PET imaging :Advantages of PET imaging Quantification (e.g. FDG-SUV, organ perfusion, metabolic rate, receptor uptake) The use of organic molecules which can take advantage of normal and abnormal human physiology and biochemistry Sensitivity and specificity greater than current diagnostic modalities in many cases Image physiology versus anatomy Can fuse with anatomic images Whole body imaging


Disadvantages :Disadvantages False Negative Reduced sensitivity for low grade malignancies such as BAC and neuroendocrine tumors Reduced sensitivity for small tumors (<5 mm) – however not significant different from characterization from conventional imaging (e.g. CT chest and small nodules) Reduced sensitivity in brain tumors diagnosis due to normal high gray matter uptake (better at recurrence/residual disease vs. scar/gliosis) False Positive Granulomatous disease (e.g. TB, fungal infection, sarcoid)


Oncology - Applications :Oncology - Applications Diagnose Stage Grade/proliferative index Monitor response Localize biopsy site Assist in RT planning Assist in identification for primary of unknown origin Assess for recurrence (scar vs. tumor) Restage


PET (FDG) Reimbursement Oncology (USA) :Lung cancer – Diagnosis, initial staging, and restaging of non-small cell lung cancer Solitary Pulmonary Nodules – Characterization Colorectal cancer – diagnosis, staging, and restaging Hodgkin’s and non-Hodgkin’s disease – initial staging and restaging Melanoma – diagnosis, initial staging, and re-staging Esophageal cancer – diagnosis, initial staging, and re-staging Breast Cancer - As an adjunct to standard imaging modalities for staging patients with distant metastasis or restaging patients with locoregional recurrence or metastasis; as an adjunct to standard imaging modalities for monitoring tumor response to treatment for women with locally advanced and metastatic breast cancer when a change in therapy is anticipated. Head and Neck cancers – diagnosis, initial staging, and re-staging Lymphoma – diagnosis, initial staging, and restaging PET (FDG) Reimbursement Oncology (USA)


Slide 18:Map adapted from http://www.worldatlas.com/webimage/countrys/canada.htm Oncology/general Dedicated Research Neuro/Cardiac dedicated Private Coincidence PET in CANADA - 2003


ECAT ACCEL - Normal :ECAT ACCEL - Normal


Slide 20:JNM 2001;42(5)S1 A Tabulated Summary of the FDG PET Literature Sanjiv S. Gambhir, Johannes Czernin, Judy Schwimmer, Daniel H. S. Silverman, R. Edward Coleman, and Michael E. Phelps


Summary of PET Literature* :Summary of PET Literature* *Bobardieri E, Crippa F. The Increasing Impact of PET. Nuclear Medicine Annual 2002;75-121 [summary of JNM 2001;42(5)S1]


Lung CancerSolitary pulmonary nodule :Lung CancerSolitary pulmonary nodule Gould et al. * 40 out of 727 studies met inclusion criteria 1474 pulmonary lesions ROC analysis with a maximum overall joint sensitivity and specificity of 91% and a current practice estimate of a sensitivity of 97% and specificity of 78% low risk (pre test 20%)  -ve PET scan  1% post test High risk (pre test 80%) -ve PET scan  14% post test * Gould et al. Accuracy of Positron Emission Tomography for Diagnosis of Pulmonary Nodules and Mass Lesions – a Meta-analysis. JAMA 2001 ;285(7):914-24 o


SPN :http://auntminnie.com SPN


Lung CancerStaging :Lung CancerStaging Pieterman et al.* Sensitivity and specificity for detecting mediastinal involvement was 91% and 86%, respectively Change in stage, compared to contemporary staging, in ~ 60% with 20% down staged and 40% upstaged Cost effectiveness studies – USA *Pieterman et al. Preoperative Staging of Non-Small Cell Lung cancer with Positron-Emission Tomography. NEJM 2000;343 (4):254-61 + http://www.vh.org/adult/provider/radiology/LungTumors/Staging + +


COST EFFECTIVENESS EXAMPLES FROM THE LITERATURE :COST EFFECTIVENESS EXAMPLES FROM THE LITERATURE Scott et al. Ann Thorac Surg 1998;66:1876-85


Lung Cancer Staging :http://auntminnie.com Lung Cancer Staging


Lung Cancer Staging :Lung Cancer Staging http://auntminnie.com


Lung Cancer :63 year old male with a mass in the right lung. biograph LSO identified peripheral lesion activity. Scan protocol: CT i.v. and oral contrast, 100 mAs, 130 kVp, 5 mm slices PET 500 MBq FDG, 60 min p.i, 2 min/bed, 6 beds, 12 min scan time Lung Cancer Data Courtesy of Hong Kong Baptist Hospital s Lung Cancer


Lung Cancer Response to therapy :Lung Cancer Response to therapy http://auntminnie.com


Lung Cancer Recurrence :Lung Cancer Recurrence Differentiating recurrence from scar Sens/Spec 98%/92% (CT 72%/95%)


CT Screening – Why? :CT Screening – Why?


CT Lung Cancer Screening :CT Lung Cancer Screening Issue of pre test probability Issue of false positives Issue of morbidity/mortality related to investigation of false positives Issue of lead and length time bias Issue of cost effectiveness


Lymphoma :Lymphoma Staging Sens/Spec  90% / 93% (CT Sens/Spec  81% / 69%) Recurrence Sens/Spec  87% / 93% [CT Sens/Spec  92% / 10%] Better than gallium for low grade tumors Whole body imaging versus regional CT Good anatomic and metabolic characterization


Diffuse Lymphoma :Diffuse Lymphoma http://auntminnie.com


Lymphoma – Therapy Response :Lymphoma – Therapy Response http://auntminnie.com


Lymphoma :Lymphoma s 23 year old female with history of lymphoma in the ovarian area. biograph LSO identified reccurence. Scan protocol: CT i.v. and oral contrast, 100 mAs, 130 kVp, 5 mm slices PET 500 MBq FDG, 60 min p.i, 2 min/bed, 6 beds, 12 min scan time Lymphoma Data Courtesy of Hong Kong Baptist Hospital


Breast Cancer :Breast Cancer Diagnosis Sens/Spec  91% / 93% Staging Sens/Spec  91% / 88% with a change in management of 24% (CT Sens/Spec  63% / 96%) Recurrence Sens/Spec  80% / 85% [CT Sens/Spec  90% / 96%]


Breast Cancer :Breast Cancer http://auntminnie.com


Head & Neck: Thyroid Cancer :Head & Neck: Thyroid Cancer 41-year-old female with follicular thyroid carcinoma. Near total thyroidectomy 4 years previous. Rise in thyroglobulin levels and whole body I-131 imaging negative. US negative. Focal recurrence suspected from whole body FDG PET image and the patient underwent local surgical resection.


Esophageal Cancer :Esophageal Cancer 64 year old male, 74 kg 388 MBq FDG 10 min/bed, 5 bed positions Esophageal Cancer Data Courtesy of Mount Vernon Hospital ECAT EXACT s


The FUTURE :The FUTURE


PET in CANADA* :PET in CANADA* BC - 2 (one private) AB – 3† (one animal or micro PET) ON – 6† QC – 2 per capita (clinical) ~ 4/10,000,000 CCOHTA, National Inventory of Selected Imaging Equipment, 1.2 Analysis by Age and Geographic Distribution of Equipment, March, 2002 † updated April, 2003


Life Sciences Branch - Industry Canada :Life Sciences Branch - Industry Canada Future Needs for Medical Imaging in Health Care Report of Working Group 1 Medical Imaging Technology Roadmap May 1, 2000 “Of 2000 PETS in the world in 1998, Europe has 40%, the USA 40% and Canada 3% (mostly for research). Accounting for the population and growth of PET, Canada would require an additional 10 units to be equivalent to Europe”


PET in MANITOBA :PET in MANITOBA Currently sending an average of 2 cases per week to Edmonton, AB Projected needs assessment* (2001 survey of oncologists and surgeons) = 2,405 or ~ 46 per week Indications have expanded since 2001 survey and current estimates would be higher Final Recommendation of the 2001 Report* was: “Planning for PET should begin in mid 2001 in order to develop clinical competencies and ensure facility planning and radiopharmaceutical logistics can be aligned for a start date of mid 2002.” Clinical Positron Emission Tomography in Manitoba – Prepared by the Provincial Nuclear Medicine Advisory Committee, April 5, 2001 – revised Jan/03


Thank You :Thank You