1. M. CHIN, D. SEWERYNIAK, M. ALKHORAYEF, N. SPYROU IN SEARCH OF EXOTIC EVENTS FOR PET: A GAMMASPHERE EXPERIMENT Department of Physics, University of Surrey, Guildford GU2 7XH, UK Argonne National Laboratory, 9700 S. Cass Avenue, Argonne IL 60439, USA

2. REPRODUCED FROM PHELPS ME ANN. REV. NUCL. PART. SCI. 2002;52:303-38 PRINCIPLES OF PET “ ’’ A POSITRON’S LIFE IS FAR MORE EVENTFUL e + EMITTER: CLINICAL SOURCE

3. Positron about to decay in flight 1 0.606 1 2 0.155,0.023,500.314 -0.122,-0.592, 0.797 Resulting photons 1 0.979 0 2 0.155,0.023 500.314 -0.311, 0.020, 0.950 2 0.649 0 2 0.155,0.023 500.314 0.282,-0.935,-0.213 NOT BACK-TO-BACK! NOT 0.511 Chin & Spyrou 2007 Nucl Instr Meth A 580:481

4. PREVIOUS WORK (previous slide) NOT 511 keV & NOT BACK-TO-BACK THIS WORK NOT TWO BUT THREE PHOTONS IN SEARCH OF EXOTIC EVENTS FOR PET: A GAMMASPHERE EXPERIMENT Monte Carlo Real !

5. e+e+ annihilate directly form positronium 70% 30% INHIBITION 2γ2γ3γ3γ 99.7% 0.27% CONVENTIONAL PET Para- positronium Ortho- positronium 25%75% 2γ2γ 3γ3γ QUENCHING

6. e+e+ annihilate directly form positronium Para- positronium Ortho- positronium QUENCHING INHIBITION AGENTS eg O 2, NO, CO 2 PROSPECTS FOR MOLECULAR IMAGING hypoxia

7. PROSPECTS FOR MOLECULAR IMAGING MEASURE 3γ/2γ YIELD FIND OUT O 2 IN BODY TISSUES? ?

8. PROPOSAL

9. REPRODUCED FROM MERCURIO K et al PHYS. MED. BIOL. 2006;51:N323-9 REFUTAL

10. REPRODUCED FROM MERCURIO K et al PHYS. MED. BIOL. 2006;51:N323-9

11. WHAT DO WE MEAN? LOOSE OR BOUND? MEASURE 3γ/2γ YIELD FIND OUT O 2 IN BODY TISSUES? ?

12. HAEMOLYSED BLOOD (HAEMOGLOBINS HAVE BEEN LIBERATED FROM RED BLOOD CELLS) SERUM (LIKE PLASMA BUT NO CLOTTING FACTORS) CELL CONCENTRATE (NO PLASMA) WHOLE BLOOD RELATIVE 3γ/2γ YIELD

13. CONFIRMS VALUES IN THE LITERATURE THE FACT THAT THEY VARY IS ENCOURAGING – AT LEAST THE METHOD IS SENSITIVE TO SOMETHING RELATIVE 3γ/2γ YIELD

14. CAN DIFFERENTIATE ‘LIFE’! CAN’T EXPECT THESE TO VARY VERY MUCH COZ THEY ARE EXPOSED TO THE ATMOSPHERE RELATIVE 3γ/2γ YIELD MOST WATER-LIKE LEAST WATER-LIKE

15. OXYGENATED DEOXYGENATED RELATIVE 3γ/2γ YIELD

16. IF O 2 WERE THE ONLY FACTOR RELATIVE 3γ/2γ YIELD EXPECTED O 2  YIELD  UNEXPECTED CONFOUNDING FACTORS

17. Local chemistry (E 1, α 1 ) (E 2, α 2 ) (E 3, α 3 ) By conservations of energy & momentum KNOWN UNKNOWNS (x 1, y 1, z 1 ) solve simultaneous eqs LINE OF RESPONSE POINT OF RESPONSE 2γ PET 3γ PET

20. source: www.phy.anl.gov source: rnc.lbl.gov source: www.nuclear.kth.se

21. GAMMASPHERE: AN UNPRECEDENTED LUXURY FOR US LUXURY #1 NEAR-4π SOLID ANGLE LUXURY #2 MULTI-DIMENSIONAL DATA WRITTEN OUT

22. GAMMASPHERE: AN UNPRECEDENTED LUXURY FOR US LUXURY #1 NEAR-4π SOLID ANGLE LUXURY #2 MULTI-DIMENSIONAL DATA WRITTEN OUT

23. DARK LINES A few detectors not working 511 keV 1022 keV summed peak

24. BEFORE COMPTON-SUPPRESSION BEFORE TIME-GATING SUPPRESSED & COINCIDENT Characteristic x-rays from bismuth spurious detectors

25. Filtering effect due to Compton-suppression Filtering effect due to coincidence-gating (More energy-dependent) FILTERED THE LEAST: FULL-ENERGY PHOTO-PEAK & SUMMED PEAK

26. 18 F-FDG 22 Na CLINICAL SOURCE MORE CHALLENGING WE USED THIS

27. VERSUS

28. GOOD CLINICAL SOURCE GOOD LABORATORY SOURCE DEAD TIME CHALLENGE

29. THIS EXTRA PEAK (not found in 18 F) - ALLOWS NORMALISATION BETWEEN 2 DATA ACQUISITIONS (we know how many disintegrations took place) - PROVIDES REFERENCE TIME TRIGGER FOR LIFETIME MEASUREMENTS (we know when the disintegration kicked-off)

30. DETECTION OF 3γ/2γ YIELDS TIME ENERGY FAST COMPONENT FREE POSITRONS SLOW COMPONENT ORTHO-POSITRONIUMS ( 3γ ) 511 keV PEAK SHORTENNED COUNTS SPREAD TO LOWER ENERGIES

31. REPRODUCED FROM LECCHI M et al Q J NUC MED MOL IMAGING 2007;51:111-26

32. REPRODUCED FROM CHERRY SR PHYS. MED. BIOL. 2004;49:R13-48

33. CONCLUSION 3γ/2γ YIELDS ARE ABLE TO DIFFERENTIATE BIOLOGICAL SAMPLES THE METHOD IS SENSITIVE TO CHEMICAL SPECIES IN THE SAMPLES 3γ/2γ YIELD DOES NOT DEPEND ON O 2 ALONE PROSPECTS NOT JUST FOR HYPOXIA-IMAGING ALONE BUT MOLECULAR IMAGING ON A WIDER SCALE FURTHER WORK TO INVESTIGATE THE DIFFERENT CONFOUNDING FACTORS PERTURBING 3γ/2γ YIELDS

34. REPRODUCED FROM HOUCHIN OB et al J. DAIRY SCI. 1939;22:241-50

35. ACKNOWLEDGEMENTS Discussions with Dr K Kacperski, who carried out the experiment while he was employed as a post-doc by the University of Surrey, are greatly appreciated This work was supported in part by the US Department of Energy, Office of Nuclear Physics, under contract No. DE-AC02-06CH11357