Positron Emission Tomography Dr. William C. Uhland Tyco-Mallinckrodt Pharmaceuticals, Maryland Heights, Missouri, USA

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1 Positron Emission Tomography Dr. William C. Uhland Tyco-Mallinckrodt Pharmaceuticals, Maryland Heights, Missouri, USA e +

2 Overview of Lecture A historical perspective A conceptual understanding of P.E.T. S.P.E.C.T. VS P.E.T. The production of P.E.T. isotopes Generator produced vs cyclotron production What can the future hold? Summary

3 A historical review

4 Paul Dirac Predicted the Existence of the Positron in 1928 Paul Dirac Predicted the Existence of the Positron in For this he shared the Nobel Prize in 1933 with Erwin Schrödinger.

5 In 1932 Carl Anderson Observed Positrons in Cosmic Rays. For this he Shared the 1936 Nobel Prize With Victor Hess.

6 A conceptual understanding of P.E.T.

7 Interaction of Positrons With Matter When encountering an electron, POSITRONIUM is formed. Positronium has an average life-time of 10-4 seconds, hence it has been well studied. Positronium behaves very much like hydrogen atoms.

8 Positronium e + e -

9 Annihilation e + e -

10 Two photons at 511 kev Annihilation γ γ

11 Two photons at 511 kev Annihilation γ γ

12 Early vestiges of P.E.T. imaging.in the beginning!

13 First Use of Positrons For Tumor Detection, Early 1950 Oxygen-15, measured with two sodium iodide detectors

14 Massachusetts General Hospital Sweet, W.H. ``The use of nuclear disintegration in the diagnosis and treatment of brain tumor'', New England Journal of Medicine 1951; 245:

15 Modern Day P.E.T. Camera

16 S.P.E.C.T. vs P.E.T.

17 Single Photon Emission Computed Tomography (S.P.E.C.T.) Can be used to get 3-D 3 D Images Less Expensive Gamma Camera Some S.P.E.C.T. drugs can be reactor produced, therefore lower production price. Most S.P.E.C.T. drugs have longer half-lives lives than P.E.T. drugs, therefore they are easier to work with.

18 Positron Emission Tomography (P.E.T.) More Expensive and Elaborate Gamma Camera Needed Than in S.P.E.C.T. All P.E.T. Pharmaceuticals Are Accelerator Produced, Therefore Higher Cost Than Reactor Produced Most P.E.T. Pharmaceuticals Have a Short Half-life life In Spite of All of this, you do get more detailed images!

19 The Production of P.E.T. Isotopes Through the use of a Cyclotron

20 P.E.T. production using cyclotron Cyclotron principles for producing F-18 F deoxy glucose, and other F-18 F labeled compounds, as well as other positron emitting radiopharmaceuticals.

21 How Does a Cyclotron Work?

22 Beam Extraction Thin Graphite Foil - + -

23 Beam Extraction Thin Graphite Foil - + -

24 Beam Extraction Thin Graphite Foil - + -

25 - Beam Extraction - Thin Graphite Foil +

26 What Does A Cyclotron Really Look Like? Really

29 Commonly Used Cyclotron Produced P.E.T. Pharmaceuticals Radionuclide Half-life life Production Method Production Energy in MeV O Minutes N-14 (d, n) O-15O 10 N Minutes O-16 (p, α) ) N-13N 15 C Minutes N-14 (p, α) ) C-11C 15 F Minutes O-18 (p,n) F-18F 15

31 Other F-18 F Pharmaceuticals 6-Fluoro DOPA 6-Fluoro-m-tyrosine 2-Fluorophenylalanine 2-Fluro-4-borono-phenylalanine Fluoroethyltyrosine Fluoro-α-methyltyrosine 6-Fluorodopamine (-) Fluoronorepinephrine

32 Other F-18 F Pharmaceuticals 16-α-Fluoroestradiol Fluoro-Setoperone Fluoro-Altanserin Fluoro-N-Methylspiperone Fluoroethylspiperone Fluoropropylspiperone Fluoromisinidazole

33 Other F-18 F Pharmaceuticals 5-Fluorouracil Fluoro-Fleroxacin Fleroxacin Fluoro-Trovafloxacin Fluoro-Lomefloxacin Fluoro-Fluconazole Fluconazole Fluoro-CFT Fluoro-CIT

34 Iodine-124 Iodine-124 Te-124(p,n)I 124(p,n)I-124, 124, Proton Energy of 10 to 20 MeV required Half-life life of 4.2 Days 23% Positron Emission Traditional Radioiodination Methods can be used, e.g., Chloramine-T, Iodogen,, Bolton- Hunter, etc.

35 Copper-64 Copper-64 Ni-64(p,n)Cu 64(p,n)Cu-64 Proton Energy of 8 to 15 MeV required Half-life life of 12.7 Hours 19.3% Positron Emission Many Biological Chelators For Copper, Allow Great Selectivity of Organs To Be Imaged

36 Generator Produced Copper-62 Generator Reaction Zn-62 β + + Cu-62 Half-life life of 9.76 Minutes 97.0% Positron Emission Many Biological Chelators For Copper, Allow Great Selectivity of Organs To Be Imaged

37 Cyclotron Production of Zinc-62 Parent of Copper-62 Zinc-62 Cu-63(p,2n)Zn 63(p,2n)Zn-6262 Proton Energy of 22 to 30 MeV required Half-life life of 9.2 Hours Generator Has a Working Life of About One Day However, No Cyclotron is Required at the Imaging Site

38 Generator Produced Gallium-68 Generator Reaction Ge-68 + e - Ga-68 Half-life life of 68 Minutes 90.0% Positron Emission Much of the Chemistry For Indium-111 can be Applied to Gallium

39 Cyclotron Production of Germanium-68 Parent of Gallium-68 Germanium-68 Ga-69(p,2n)Ge 69(p,2n)Ge-6868 Proton Energy of 12 to 30 MeV required Half-life life of 272 Days Generator Has a Working Life Over a Month No Cyclotron is Required at the Imaging Site

40 What does the future hold for P.E.T. in Spain?

41 Future considerations Regulations in Spain related to Nuclear Medicine Feasibility for P.E.T. within hospital settings. Feasibility for options within urban and rural settings. Mobile P.E.T. imaging Other issues?

42 Summary Today we have covered a lot in a short time! To summarize, we reviewed: A historical perspective A conceptual understanding of P.E.T. S.P.E.C.T. VS P.E.T. The production of P.E.T. isotopes Generator produced vs cyclotron production What can the future hold within Spain?

43 Contact information Dr. William C. Uhland Senior Chemist Mallinckrodt Inc Wagner Place Maryland Heights, MO

CLINICALLY USEFUL RADIONUCLIDES:

CLINICALLY USEFUL RADIONUCLIDES: INTRODUCTION It is important that Nuclear Medicine Technologists be familiar with the imaging properties of all commonly used radionuclides to insure correct choice of isotope for a particular study as