Generacin de Istopos Emisores de Positrones y Rayos

Generación de Isótopos Emisores de Positrones y Rayos Gamma para Imagen Médica Joaquin L. Herraiz 1, Luis M. Fraile 1, José M. Udías 1 1 Universidad Complutense de Madrid, Grupo de Física Nuclear – CEI Moncloa, Madrid, Spain herraiz@nuclear. fis. ucm. es

Positron Emission Tomography (PET) DETECTION OF 2 GAMMA RAYS IN COINCIDENCE IMAGE OF THE BIODISTRIBUTION OF THE RADIOTRACER

Imaging 2 PET tracers in 1 Acquisition PROBLEM: All annihilation gamma-rays have the same energy: 511 ke. V PROPOSED SOLUTION: m. PET 1) Use of (β+) & (β+γ) Emitters 2) Detect Triple Coincidences 3) Reconstruction & Separation TRACER A : labeled β+ emitter Standard (e. g. , 18 F, 13 N) TRACER B : labeled β+γ emitter Non-standard (e. g. , 124 I, 76 Br) A. Andreyev et al. PMB 2011 E. Lage et al Med. Phys, 2015 J. Cal-Gonzalez et al. PMB 2015

β+ Emitters (16. 2 h) 3. 4 ps 12. 3 ps Lovqvist A et al. , J. Nucl. Med. 1997

+ β Emitters 82 Rb 52 m. Mn 60 Cu 94 m. Tc 110 m. In 120 I 44 Sc 86 Y 76 Br 72 As 124 I Half-life β+ yield (%) Main Prompt γ [ke. V] & (β+ γ / β+ yield) Production 1. 27 m 21. 1 m 23. 7 m 52. 0 m 1. 15 h 1. 35 h 3. 97 h 14. 7 h 16. 2 h 1. 08 d 4. 18 d 95 97 93 70 62 46 94 33 26 88 23 777 (13%) 1434 (96%) 1333 (88%) 871 (96%) 658 (99%) 560 (72%) 1157 (100%) 1080 (85%) 559 (58%) 834 (79%) 602 (51%) Generator Cyclotron Generator Large t 1/2

Detection of Triple Coincidences, Image Reconstruction and Separation PET scanner Doubles Standard Reconstruction Iterative image Separation Triples Tracer A: β+ Tracer B: β+γ VLOR Reconstruction Image A Image B

Production of 60 Cu, 52 m. Mn and 94 m. Tc Isotope Halflife Decay Main Prompt Mode (Me. V) (%) and Yield (%) 60 Cu + 23. 4 m (93%) 52 m. Mn + 21. 1 m (95%) 94 m Tc + (72%) 53 m 1. 333 (80%), 1. 760 (52%) 1. 434 (98%) 0. 871 (94%) Target Nat. Ni (26. 16% 60 Ni) Nat. Cr (83. 8% 52 Cr) Nat. Mo (9. 12% 94 Mo) Production Energy Threshold Q (Me. V) Cross – Section (barn) @ 10 Me. V 60 Ni(p, n)60 Cu 6. 91 0. 25 52 Cr(p, n)52 m. Mn 5. 49 0. 35 94 Mo(p, n)94 m. Tc 5. 04 0. 55

Experimental Setup: • • The Cockcroft-Walton 5 MV tandetron accelerator at CMAM in Madrid was used to obtain a proton beam of 10 Me. V with intensities 1 μA. As a proof-of-concept experiment, low activation was pursued (< 2 μCi).

Experimental Setup: • Solid thin target foils of natural Ni, Cr and Mo, mounted on top of Ta backing, were activated for around 1 min. • A HPGe detector, with calibrated efficiency, was used to identify and measure the -rays from the activated foils to obtain the production yield. Target Foils Natural Ni Natural Cr Natural Mo

511 1484 1333 1760 511 871 HPGe Spectrum of the activated natural Ni, Cr and Mo foils at the end of bombardment

RESULTS: Thickness Target (mm) 1) 2) 3) 4) 5) 6) 7) Total Current (n. C) Expected Measured Irradiation Yield EOB Time (s) (m. Ci/u. Ah) Nat. Ni 0. 200 100. 3 10 11. 91 12. 11 Nat. Cr 3. 175 506. 7 10 100. 27 80. 35 Nat. Mo 0. 100 3000 60 3. 63 5. 34 JANIS Book of proton-induced cross-sections OECD NEA Data Bank, N. Soppera, E. Dupont, M. Bossant, (2012). L. P. Szajek et al. , Production and radioassay of Tc-94 m for PET studies. Radiochim. Acta 91, 613– 616 (2003) Rösch, F. et al. , Nuclear data relevant to the production of the positron emitting technetium isotope 94 m. Tc via the 94 Mo(p, n)-reaction. Radiochim. Acta 62, 115 (1993). Rösch, F. et al. , High purity production of the positron emitting technetium isotope 94 m. Tc. J. Labelled Compd. Radiopharm. 35, 267 (1994). Qaim SM. Production of high purity (94 m)Tc for positron emission tomography studies. Nucl Med Biol. 2000 May; 27(4): 323 -8. Deborah W. Mc. Carthy et al. High Purity Production and Potential Applications of Copper-60 and Copper-61. Nuclear Medicine & Biology, Vol. 26, pp. 351– 358, 1999 H. I. West et al. , 52 Cr(p, n)52 Mng, m and 52 Cr(d, 2 n)52 Mng, m excitation functions. PRC, vol 35, no 6, (1987).

RESULTS: DOUBLE COINCIDENCES A DOUBLE+TRIPLE COINCIDENCES B C (Left) Picture of the mouse in the bed of the scanner with the foils located in the armpit and on the neck. (Right) Reconstructed m. PET images. (A) Image reconstructed using only double coincidences. (B, C) Reconstructed separated images of 68 Ga and 94 m. Tc using double and triple coincidences.

Summary & Conclusions: • Production of the β+γ emitters 60 Cu, 52 m. Mn & 94 m. Tc in quantities sufficient for preclinical studies ( m. Ci) with a 10 Me. V proton beam is feasible • The production yields measured are in agreement with the available references (taking into account their large uncertainties below 10 Me. V), although the differences in 52 m. Mn are significant. • It was possible to separate 94 m. Tc from 68 Ga in a PET scanner based on their different emission. • Other studies are being considered, and collaborations with other groups are welcome.

Acknowledgements This work was supported in part by Comunidad de Madrid (Spain) through the Madrid –MIT M+Visión Consortium, the COFUND of the Seventh Framework Program of the European Union. CMAM (http: //www. cmam. uam. es) Angel Muñoz University Autónoma of Madrid Eduardo Lage University Carlos III of Madrid and Hospital Gregorio Marañon Juan José Vaquero Manuel Desco

124 I-MIBG Multiplexed PET 18 F-FDG