Overview of PET/CT in Oncology

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This presentation deals with the overview of PET/CT, including what PET/CT is, principle of PET/CT imaging, what kind of radiopharmaceutical used, and mechanism of uptake, as well as how PET/CT images are displayed.

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Overview of PET/CT in Oncology

  1. 1. Jiraporn Sriprapaporn Division of Nuclear Medicine Department of Radiology Faculty of Medicine Siriraj Hospital Mahidol University PET/CT in Oncology Last Updated on 24 January 2016
  2. 2. Jiraporn_PET/CT in Onco 2016 PET/CT in Oncology  Part 1. Overview of PET/CT imaging  Part 2. How to perform and interpret F-18 FDG PET/CT imaging  Part 3. Clinical applications of F-18 FDG PET/CT imaging in oncology
  3. 3. Jiraporn_PET/CT in Onco 2016 PET/CT Imaging in Oncology Overview about PET & PET/CT Introduction PET, PET/CT scanners PET radiopharmaceuticals : F-18 FDG*** Mechanism of F-18 FDG uptake Principle of F-18 FDG PET- CT imaging Radiation dose from PET/CT Procedure Guideline for F-18 FDG imaging (SNMM) Indications Patient preparation Patient information Technique Interpretation: Normal Normal variants Artifacts & pitfalls (false positive & false negative)
  4. 4. Jiraporn_PET/CT in Onco 2016 Part 2: Clinical indications for PET/CT imaging in oncologic patients. • PET/CT imaging in certain types of cancer  Single pulmonary nodule  Lung cancer-NSCLC  Colorectal cancer  Lymphoma  Head and neck cancer Thyroid cancer  PET/CT reimbursement for F-18 FDG PET/CT in Thailand  Lung cancer-NSCLC for staging  Colorectal cancer for restaging (suspected tumor recurrence)
  5. 5. Jiraporn_PET/CT in Onco 2016 Overview of PET & PET/CT  Introduction  PET, PET/CT scanners  PET radionuclides/ radiopharmaceuticals: F-18 FDG***  Mechanism of F-18 FDG uptake  Principle of F-18 FDG PET-CT imaging  Radiation dose
  6. 6. Jiraporn_PET/CT in Onco 2016 Jiraporn_PET/CT in Onco 2016 Introduction  PET = Positron Emission Tomography  Evaluation of in-vivo metabolic imaging, by using positron emitters.
  7. 7. Jiraporn_PET/CT in Onco 2016 PET-CT in Oncology: Advantages  PET & CT imaging  physiologic & anatomic info  Whole-body evaluation  High sensitivity  High resolution imaging  Good patient tolerance  Suitable for repeated imaging Normal vs Pathologic
  8. 8. Jiraporn_PET/CT in Onco 2016 Weber WA et al. (2008) Technology Insight: advances in molecular imaging and an appraisal of PET/CT scanning Nat Clin Pract Oncol doi:10.1038/ncponc1041 Figure 1 Number of PET/CT and PET scans performed in the US per year from 2000 to 2006, with an estimate (*) for 2007
  9. 9. Jiraporn_PET/CT in Onco 2016 PET Centers in U.S.  According to the 2012 PET Imaging Market Summary Report published by International Marketing Ventures, PET and PET/CT studies were performed at over 2,200 U.S. locations  Per a 2011 census, a total of 1,853,700 clinical PET/CT and PET studies were performed in US., with oncology, cardiology, neurology, and others constituting 94% (1,736,800), 3% (53,300), 3% (58,000), and < 1% (5,600), respectively (Surasi DS. JNMT 2014;42:5-13). • In 2009, almost 2000 PET centers in U.S. • Deep blue: > 100 centers [Data from Buck AK, JNMT 2010;38(1):6-17] TX CA PA-NY FL
  10. 10. Jiraporn_PET/CT in Onco 2016 Hybrid Imaging: PET/CT Carries the Load Greg Freiherr, Disclosures May 17, 2011  In 2008, oncology accounted for about 94% of all PET/CT scans done in the United States.  The remaining 6% was split evenly between cardiology and neurology, according to IMV.  Four types of cancer accounted for the oncology scans: lung (27%), Hodgkin's disease (19%), breast (17%), and colorectal cancer (12%). http://www.medscape.com/viewarticle/742498 Siriraj H: Lung cancer, CRC, lymphoma (NHL >HL)
  11. 11. Jiraporn_PET/CT in Onco 2016 4 Factors Facilitate Widespread Use of FDG PET-CT Imaging 1.The development of PET scanners with a large field of view for whole-body scanning;  great impact for the detection of distant metastatic sites in cancer patients. 2.The commercial availability of F-18 FDG for hospitals that do not have a cyclotron. 3.The introduction of a PET camera and a CT scanner into a single setting (integrated PET/CT). 4.The approval of reimbursement for PET/CT using F-18 FDG for most oncologic studies. Endo K et al. 2006
  12. 12. Jiraporn_PET/CT in Onco 2016 PET/CT Clinical Applications
  13. 13. Jiraporn_PET/CT in Onco 2016 Cancer Statistics/Risk  Lifetime Risk of Developing Cancer:  Approximately 39.6 % of men and women will be diagnosed with all cancer sites at some point during their lifetime, based on 2010-2012 data. Source: National cancer Institute: http://seer.cancer.gov/statfacts/html/all.html
  14. 14. Jiraporn_PET/CT in Onco 2016 Risk of developing cancer during lifetime MALE % 1 in All invasive sites 43.31 2 Prostate 15.02 7 Lung and bronchus 7.43 13 Colon and rectum 4.84 21 Bladder (includes in situ) 3.83 26 Melanoma of the skin 2.56 39 Non-Hodgkin lymphoma 2.36 42 Kidney and renal pelvis 2.04 49 Leukemia 1.7 59 Oral cavity and pharynx 1.55 65 Pancreas 1.52 66 FEMALE % 1 in All invasive sites 37.81 3 Breast 12.33 8 Lung and bronchus 6.17 16 Colon and rectum 4.49 22 Uterine corpus 2.73 37 Non-Hodgkin lymphoma 1.91 52 Thyroid 1.68 60 Melanoma of the skin 1.61 62 Pancreas 1.48 68 Ovary 1.33 75 Kidney and renal pelvis 1.19 84
  15. 15. Jiraporn_PET/CT in Onco 2016 Cancer Statistics 2015 Siegel RL 2015 1. Prostate 2. Lung 3. Colon 1. Breast 2. Lung 3. Colon Lung
  16. 16. Jiraporn_PET/CT in Onco 2016 Introduction
  17. 17. Jiraporn_PET/CT in Onco 2016 Values of PET  Permits cost-effective, whole-body metastatic survey.  Avoids biopsy for low-grade tumors.  Avoids unnecessary or futile surgery.  Permits early change in course of ineffective CMT.  Permits noninvasive differentiation of active tumors from postRx fibrosis.
  18. 18. Jiraporn_PET/CT in Onco 2016 Overview of PET & PET/CT  Introduction  PET, PET/CT scanners  PET radionuclides/ radiopharmaceuticals: F-18 FDG***  Mechanism of F-18 FDG uptake  Principle of F-18 FDG PET-CT imaging  Radiation dose
  19. 19. Jiraporn_PET/CT in Onco 2016 Instrument  1952  The first gamma camera was reported by Hal Anger in 1952  1972  The first CT scanner was invented by British engineer Godfrey Hounsfield of EMI Laboratories, England and by South Africa- born physicist Allan Cormack of Tufts University, Massachusetts. (Hounsfield and Cormack were later awarded the Nobel Prize)  1973 The first PET camera was built for human studies by Edward Hoffman, Michael M. Ter-Pogossian, and Michael E. Phelps at Washington University  1975  The first commercial PET scanner  1977  The first whole-body PET scanner  1977  The first MRI for human body was produced by Raymond Damadian, a physician at State University of New York (SUNY) Brooklyn,.  1980  The first commercial MRI in March 1980 (Melville Company, NY). •Edward J. Hoffman •Michel M. Ter- Pogossian •Michael E. Phelps
  20. 20. Jiraporn_PET/CT in Onco 2016  1998  The 1st prototype PET/CT scanner was invented by Dr. Ron Nutt and Dr. David Townsend  1999  PET/CT was approved by FDA in Oct 1999.  Medical Inventions of the year 2000 by Time Magazine  2001, PET/CT = ”Product of the Year” by Frost and Sullivan.  2001  commercially available The U.S. Food and Drug Administration approved the combined PET/CT scanner in October 1999.
  21. 21. Jiraporn_PET/CT in Onco 2016 Suggested Reading
  22. 22. Jiraporn_PET/CT in Onco 2016 PET SCANNERS  Dedicated PET Scan  Dual-head coincidence PET scan  PET/CT scan  PET/MRI (SNM Meeting 2007, FDA approved in 6/2011)
  23. 23. Jiraporn_PET/CT in Onco 2016 3 vendors* SIEMENS PHILIPS GE Healthcare Hitachi Medical Toshiba
  24. 24. Jiraporn_PET/CT in Onco 2016 PET-CT Scanners
  25. 25. Jiraporn_PET/CT in Onco 2016 PET/CT-GE Healthcare  Optima* PET/CT 560  Discovery PET/CT 690 : 64 slices LYSO (Lutetium based scintillator)  Discovery PET/CT 610 : LYSO  Discovery STE : 16 slices BGO  Discovery VCT
  26. 26. Jiraporn_PET/CT in Onco 2016 Current PET/CT Scanners At the end of 2014
  27. 27. Jiraporn_PET/CT in Onco 2016 Table 11.2 Properties of scintillation crystals used in positron emission tomographic (PET) scanners Properties/Crystals NaI(Tl) BGO GSO:Ce LSO:Ce LYSO:Ce Density (gm/cm3) 3.67 7.13 6.7 7.4 7.1 Effective atomic number (Z) 51 74 59 66 64 Linear attenuation coefficient (1/cm) 0.34 0.92 0.62 0.87 0.86 Light yield (% NaI[Tl]) 100 15 30 75 75 Decay time (ns) 230 300 65–60 40 41 Emission maximum (nm) 410 480 440 420 420 Hygroscopic Yes No No No No Photoelectric effect (%) 17 40 25 32 33 Refractive Index 1.85 2.15 1.85 1.82 1.81 Basic Sciences of Nuclear Medicine By Magdy Khalil, Springer 2011
  28. 28. Jiraporn_PET/CT in Onco 2016 PET/CT in Thailand  1st at Watanosot Hosp: PHILIPS Gemini GXL 16SL, GSO [Nov 2005]+CYC  2nd at Chulabhorn cancer center: SIEMENS Biograph 16, LSO [2005]+ CYC  3rd at Chulalongkorn Hospital: SIEMENS Biograph 16, LSO  4th at Siriraj Hospital-GE Discovery STE 16, BGO [November 2006]  5th at Bumrungrad Hosp: SIEMENS Biograph TruePoint 64, LSO [18-6-08-http://www.thaipr.net]  6th at Ramathibodi Hospital-PHILIPS Gemini TF, LYSO [May 2011]  SiPH : GE Discovery 690 16 SL, LYSO [Dec 2012]+CYC  Khonkaen U. :GE Discovery 690 16 SL, LYSO  Chieng-mai U. Biograph 128 mCT [22 May 2014]+CYC *CYC = Cyclotron 2 1 3
  29. 29. Jiraporn_PET/CT in Onco 2016 PET/CT in Thailand Order Start Hospital Gov/ Private PET –CT Scanner Vendor Model PET Crystal CT Cyclotron 1 2005 Watanosot H P PHILIPS Gemini GXL GSO 16 ACSI, 19 MeV 2 2005 Chulabhorn cancer center G SIEMENS Biograph LSO 16 GE, 16 MeV 3 2006 Chulalongkorn H G SIEMENS Biograph LSO 16 No 4 2006 Siriraj H G GE STE BGO 16 Sumitomo, 20 MeV 5 2008 Bumrungrad H P SIEMENS Biograph True Point LSO 64 No 6 2011 Ramathibodi H G PHILIPS Gemini TruePoint LYSO 64 No 7 2012 SiPH H P GE Discovery 610 LYSO 16 No 8 2014 Khonkaen U G GE Discovery 610 LYSO 16 No 9 2014 Chieng Mai U G SIEMENS Biograph mCT LSO 128 Sumitomo, 20 MeV
  30. 30. Jiraporn_PET/CT in Onco 2016 Biograph 128 mCT  It offers 2 mm uniform resolution throughout the field of view (FOV).  And with the TrueV extended field of view package, you can double Biograph mCT’s PET count rate to reduce acquisition time or injected dose by 50%.
  31. 31. Jiraporn_PET/CT in Onco 2016 Overview of PET & PET/CT  Introduction  PET, PET/CT scanners  PET radionuclides/ radiopharmaceuticals: F-18 FDG***  Mechanism of F-18 FDG uptake  Principle of F-18 FDG PET-CT imaging  Radiation dose
  32. 32. Jiraporn_PET/CT in Onco 2016 PET Radionuclides  Positron-emitting radionuclides (emit positron (e+) from Nu (p excess)  Relatively short half-lives and high radiation energies (compared to general NM imaging)  Produced by cyclotron* or generators
  33. 33. Jiraporn_PET/CT in Onco 2016 Principal Positron Emitters Radionuclides Production Physical T1/2 C-11 Cyclotron 20 min N-13 Cyclotron 10 min O-15 Cyclotron 2 min F-18 Cyclotron 110 min Ga-68 Generator 68 min Rb-82 Generator 75 sec
  34. 34. Jiraporn_PET/CT in Onco 2016 Production of PET Radionuclides  11C 14N(p,a)11C  13N 16O(p,a)13N  15O  15N(p,n)15O, 14N(d,n)15O  18F  18O(p,n)18F, 16O (3He,p) 18F, 20Ne (d,x)18F  82Rb  82Sr/82Rb generator T1/2=1.52 min. [82Sr T1/2= 25 days]  68Ga  68Ge/68Ga generator T1/2= 68 min. [68Ge T1/2= 270.8 days]  124I  124Te(p,n)124I T1/2=4.16 days 18O enriched water
  35. 35. Jiraporn_PET/CT in Onco 2016 Physical Properties of PET Radionuclides Vallabhajosula S, SNM 2011
  36. 36. Jiraporn_PET/CT in Onco 2016 Development of F18-FDG  Alfred P. Wolf, a chemist [GER] at Brookhaven National Laboratory known as the father of organic radiochemistry, a field that links medicine and chemistry.  In 1976, Wolf and colleagues developed and used a radiotracer called F-18 fluorodeoxyglucose to generate the first functional map of the human brain at work. Tatsuo Ido F-18 FDG is the most commonly used tracer for PET/CT scanning, received FDA approval for cancer imaging in 2000 & for all cancer type in 2005
  37. 37. Jiraporn_PET/CT in Onco 2016 F-18 FDG  F-18 FDG (F-18-2-fluoro-2-deoxy-D-glucose) or fluorodeoxyglucose (glucose analogue)  Replace OH group to be F-18  Measure glucose metabolism
  38. 38. Jiraporn_PET/CT in Onco 2016 FDA-Approved PET Radiopharmaceuticals Vallabhajosula S, SNM 2011 NDA = New Drug Application
  39. 39. Jiraporn_PET/CT in Onco 2016 FDA-Approved PET Radiopharmaceuticals Radiopharms Year of approval Clinical Indication F-18 Fluoride 1972 Bone imaging Rb-82 1992 Myocardial perfusion F-18 FDG 1994 Epileptic foci F-18 Fluoride 2000 Bone Imaging N-13 NH3 2000 Myocardial perfusion F-18 FDG 2000 Epileptic foci in brain Myocardial glucose metabolism Tumor glucose metabolism F-18 FDG 2005 Alzheimer’s disease (AD) and Fronto-temporal dementia (FTD)
  40. 40. Jiraporn_PET/CT in Onco 2016 Vallabhajosula S, SNM 2011 FDG vs Non-FDG Radiopharms
  41. 41. Jiraporn_PET/CT in Onco 2016 Overview of PET & PET/CT  Introduction  PET, PET/CT scanners  PET radionuclides/ radiopharmaceuticals: F-18 FDG***  Mechanism of F-18 FDG uptake  Principle of F-18 FDG PET-CT imaging  Radiation dose
  42. 42. Jiraporn_PET/CT in Onco 2016 F-18 FDG  F-18 FDG (F18-2-fluoro-2-deoxy-D-glucose) or fluorodeoxyglucose (Glucose analogue)  Glucose metabolism  FDG enters the cells using the same pathway as glucose (glucose transporter proteins, GLUT) [R23: Mochizuki T, et al. JNM 2001] but is not used in glycolysis and is metabolically trapped inside the cells after phophorylation (FDG- 6-phosphate).  FDG is excreted in large quantities by kidneys unlike glucose.
  43. 43. Jiraporn_PET/CT in Onco 2016 Jiraporn_PET/CT in Onco 2016 FDG Metabolism Enz1 = Hexokinase – Phosphorylation GLUT = Glucose transpoter Enz2= Glucose-6-phosphatase Tumor cells  higher glycolytic rate than normal tissue. 1 1 2 2 Glycolysis Glycolysis GLUT GLUT G-6-P isomerase (Buck AK JNM 2004)
  44. 44. Jiraporn_PET/CT in Onco 2016 Glucose Transporters
  45. 45. Jiraporn_PET/CT in Onco 2016 Mechanism of F-18 FDG Uptake Malignant cells have increased glucose utilization due to  Over expression of membrane glucose transporter receptors, especially GLUT-1 and GLUT-3 on surface of tumor cells.  Increased hexokinase activity  Decreased level of glucose-6-phosphatase
  46. 46. Jiraporn_PET/CT in Onco 2016 Overview of PET & PET/CT  Introduction  PET, PET/CT scanners  PET radionuclides/ radiopharmaceuticals: F-18 FDG***  Mechanism of F-18 FDG uptake  Principle of F-18 FDG PET-CT imaging
  47. 47. Jiraporn_PET/CT in Onco 2016 Principle of PET Imaging  Detecting (indirectly) positron emission via the detection of both annihilation photons (511 keV) that occur and hit opposite detectors simultaneously (within coincidence time window ~ 10 ns)  Spatial resolution ~ 4-5 mm FWHM annihilation
  48. 48. Jiraporn_PET/CT in Onco 2016 Positron Range & Image Resolution  The distance that the positron will travel in tissue before annihilation depends on the energy of the positron,  this distance being about 1 mm in the case of the positrons emitted by F-18 and about 1.5 mm in the case of O-15. Isotope Half-life (min) Maximum positron E (MeV) Positron range in water (FWHM- mm) Production method 11C 20.3 0.96 1.1 cyclotron 13N 9.97 1.19 1.4 cyclotron 15O 2.03 1.70 1.5 cyclotron 18F 109.8 0.64 1.0 cyclotron 68Ga 67.8 1.89 1.7 generator 82Rb 1.26 3.15 1.7 generator http://depts.washington.edu/nucmed/IRL/pet_intro/intro_src/section2.html
  49. 49. Jiraporn_PET/CT in Onco 2016 Steps for PET-CT Imaging  Production of positron-emitting Rdn.  Labeling a selected compound with a positron-emitting Rdn.  Administration into a patient (IV, inhalation)  Imaging the patient  Reconstruction & display (Quantitation) PET IMAGING CYCLOTRON PET-CT IMAGES PET-CT SCANNER RADIOPHARM PATIENT
  50. 50. Jiraporn_PET/CT in Onco 2016 PET-CT Imaging CT PET  Scout CT-Topogram  CT-low mA  PET-Non AC  PET-AC  PET(AC)+CT
  51. 51. Jiraporn_PET/CT in Onco 2016 Sequences of PET/CT imaging  Topogram (scout)  CT scan- skull base to midthigh  PET scan (NAC)  PET scan (AC)- reconstruction  PET/CT image fusion  MIP image (maximal intensity projection) 3 planes
  52. 52. Jiraporn_PET/CT in Onco 2016 Topogram Sequences of PET/CT imaging
  53. 53. Jiraporn_PET/CT in Onco 2016 Estimated Radiation Dose  About 50% of F-18 FDG is excreted in the urine at 2 hrs  Estimated rad dose at bladder wall is the highest organ,. [Oehr et al. 2004]  1 rad for each chest/abd/pelvic CT scan. The Essentials:  Dose rate of F-18 = 6 folds Tc-99m  Effective dose 1 mSv/mCi F-18 FDG  F-18 FDG accumulates in breast tissue but not significantly secreted into breast milk, withdraw breast feeding for 8 hrs. to reduce rad to the infant.[close contact]
  54. 54. Jiraporn_PET/CT in Onco 2016 Radiation Exposure  The radiation dose of FDG is approximately 2 × 10−2 mSv/MBq according to ICRP publication 106 [28], i.e. about 3–4 mSv for an administered activity of 185 MBq. (5 mCi) [EANM Guideline] Authors F-18 FDG PET Dose (mSv) CT Dose (mSv) Total PET/CT RAD Dose Kaushik A, 2013 PMID 24125986 -Female -Male 14.4 11.8 Khamwan K, 2010 4.40 14.45 18.85 Huang B, 2009 PMID 19251940 -Female -Male 6.40 6.60 19.10 19.70 25.5 26.3 Quan V, 2007 7 18 25 Brix G, 2005 15809483 25
  55. 55. Jiraporn_PET/CT in Onco 2016
  56. 56. Jiraporn_PET/CT in Onco 2016 Jiraporn_PET/CT in Onco 2016  18F-FDG PET/CT examination at King Chulalongkorn Memorial Hospital  PET/CT system, LSO HI-REZ, CTI/Siemens Medical System  FDG is 5.55 MBq/kg; CT 120 kVp, current varied  The average whole-body effective doses from PET and CT were 4.40 ± 0.61 and 14.45 ± 2.82 mSv, respectively, resulting in the total patient dose of 18.85 mSv. http://rpd.oxfordjournals.org/content/141/1/50.full Radiat Prot Dosimetry (2010) 141 (1): 50-55. The determination of patient dose from 18F-FDG PET/CT examination
  57. 57. Jiraporn_PET/CT in Onco 2016 Overview of PET/CT: Summary  PET/CT imaging is most widely used in the field of oncology.  PET/CT has better accuracy than PET or CT alone.  F-18 FDG is the most common radiopharmaceutical used for oncologic applications.  Most of PET emitters are produced in the cyclotron unit.  Drawbacks of PET/CT in Thailand include few PET centers available and relatively high cost with limited reimbursement.

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