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Diagnostic Nuclear Physics in Medicine

Diagnostic Nuclear Physics in Medicine. Thomas J. Ruth UBC/TRIUMF PET Program TRIUMF, Fall 2004. Diagnostic medicine tries to look into the body to see what is happening, in life and in death. Rembrandt - anatomy lesion. How can we probe the human body without a knife?

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Diagnostic Nuclear Physics in Medicine

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  1. Diagnostic Nuclear Physics in Medicine Thomas J. Ruth UBC/TRIUMF PET Program TRIUMF, Fall 2004

  2. Diagnostic medicine tries to look into the body to see what is happening, in life and in death. Rembrandt - anatomy lesion

  3. How can we probe the human body without a knife? But first some fundamental ideas that are needed to understand this topic.

  4. Size matters! How big is Avogadro’s number – 6.02 x 1023? Each Smartie – 1 cm3 or 1 mL 1 mole of Smarties = 6 x 1023 mL Assume a truck with a capacity of 90 m3 (10x3x3) = 9 x 107 mL The number of trucks needed – 6 x 1015 If each truck is 13 m long, that means that lined up they would be 7.8 x 1013 km in length or 200 million earth to moon distances.

  5. 1 grain of salt – 0.12 mg = 2 x 10-6 moles (or 2 micromoles) = 3 x 1017 molecules This issue will come up later in our discussion of tracers.

  6. Normal chest x-ray X-ray images produce shadows based on density of matter.

  7. CT image of the brain

  8. Magnetic Resonance Imaging (MRI)

  9. All of the images shown thus far look at structure. Many of these images would look the same in a living person or in a cadaver. What about function?

  10. Why Use PET Imaging? • PET imaging is capable of providing quantitative information about biochemical and physiological processes, in vivo.

  11. Tracer Principle • Tracer behaves in a similar way to the components of the system to be probed. • Tracer does not alter the system in any measurable fashion. • Tracer concentration can be measured.

  12. Basic Principles of PET • Based on tracer principle. • Tracer labeled with positron emitting radioisotope. • Positron decay. • Coincidence detection of annihilation radiation.

  13. Positron Annihilation Positron emitter Positron range 1 - 10 mm Neighboring atom g #2 g #1 Gamma ray range 10 mm -  180°

  14. Positron Emission Tomography detector #2 g #2 g #1 detector#1

  15. PET measures concentration of radioactivity 1) Gamma rays escape from the body: Allows external detection. 2) Two gamma rays are emitted at 180° when a positron annihilates: The annihilation occurred somewhere along the line of response (LOR) between the 2 detectors.

  16. PET measures concentration of radioactivity 3)Regions with greater radioactivity levels produce more LORs: Concentration of radioactivity can be measured and quantified.

  17. How do you go from detecting events to an image?

  18. Corrections necessary for quantitative PET (mCi/cc tissue) • Scatter correction • Attenuation correction • Random subtraction • Normalization • Calibration

  19. CH2OH CH2OH O O OH OH OH OH OH OH OH F* Fluorodeoxyglucose (FDG) Glucose

  20. FDG Uptake and Retention Cells Blood Glycolysis Glucose Glucose Glucose-6P FDG FDG FDG-6P

  21. Focus of the PET Program has been on the Brain

  22. The brain, my second most favorite organ. Woody Allen

  23. Goals of the Pacific Parkinson’s Research Centre • Determine the origins of PD • Follow natural history of disease (Progression) • Develop treatments • Control complications of treatment

  24. Preliminary epidemiological data

  25. Clusters • CBC, Vancouver – 4/120 • Community college, eastern BC – 4/32 • Garment factory, Montreal – 3/8 200-300 per 100,000 population. ~ 1% in population aged over 60 years.

  26. DA

  27. DAT

  28. Radiopharmaceuticals • Dopamine system • 18F-FDOPA • 11C-Methylphenidate • 11C-Dihydrotetrabenazine • 11C-Raclopride • 11C-Sch23390 NB – 11C high specific activities (10 mCi @ 10 Ci/mmole ~ 1014 molecules)

  29. For PET research you need clever and gifted chemists! Photo by Will Brown/courtesy of Chemical Heritage Foundation

  30. Controls p=0.0274 MPTP-exposed Exposure 1st scan 2nd scan

  31. 11C-DTBZ 11C-SCH 23390 11C-MP D1R VMAT2 Tyr DOPA DA D2/D3R DAT 11C-RACLOPRIDE 18F-FD 18F-FD 11C-MP 11C-DTBZ

  32. DTBZ vs FDOPA DTBZ vs MP 11C-DTBZ 11C-SCH 23390 (n = 35) (n = 35) 100 100 11C-MP D1R 75 75 VMAT2 MP (% Normal) 50 50 FDOPA (% Normal) Tyr DOPA DA D2/D3R 25 25 DAT 11C-RACLOPRIDE 0 0 0 25 50 75 100 0 25 50 75 100 18F-FD DTBZ (% Normal) DTBZ (% Normal) Investigation of disease compensatory mechanisms Lee et al 2000

  33. The importance of isomeric purity. VMAT2 - 11C-dihydrotetrabenazine Multiple chiral centres

  34. In vivo assessment of endogenous DA concentration DA DA DA 11C-Raclopride Endogenous DA competes with raclopride for the D2 receptor

  35. Apomorphine-induced changes in RAC binding (putamen) 3 Error Bars: ± 1 Standard Error(s) 2.5 2 1.5 1 .5 0 APO_0 APO_1 APO_2

  36. Unlocking the mysteries of the brain!

  37. Can you focus this please? Circa 1976, BNL/UPenn

  38. Yes! • 25 years later • And 100’s M $

  39. Crystal material: LSO/LYSO Crystal size 2.1 x 2.1 x 10 mm3

  40. UBC/TRIUMF HRRT

  41. High Resolution Research Tomograph • 119,000 detector elements • 4,000,000,000 lines of response • > 1Gbyte of data per image frame

  42. Significant Results Beyond UBC/TRIUMF PET FDG Supply (b-HC!) 18F- FDG mPET PET/CT Vendor not selected!

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