Production of non-conventional high specific activity radionuclides for

Production of non-conventional high specific activity radionuclides for biomedical, toxicological and environmental purposes Flavia Groppi, Mauro Bonardi, Luigi Gini Dipartimento di Fisica – UNIMI and INFN Sezione di Milano L. A. S. A. Via F. lli Cervi, 201 20090 Segrate (MI) Enzo Menapace Divisione per le Tecnologie Fisiche Avanzate – ENEA, Bologna Zeev Alfassi Department of Nuclear Engineering, Ben Gurion University, Be’er Sheva , Israel Boris Zhuikov Institute for Nuclear Research of Russian Academy of Sciences, Moscow, Russia Kamel Abbas, Uwe Holzwarth, Neil Gibson Institute for Health and Consumer Protection, JRC, EC, Ispra (Va) 13 October 2005 Mauro. Bonardi@mi. infn. it Highligths_Physics Flavia. Groppi@mi. infn. it

Main Research Fields • Studies of non-conventional high specific activity radionuclides by Cyclotron and Nuclear Reactor • Quality Control of radiopharmaceutical compounds labelled with short- lived and high specific activity radionuclides: by , and spectrometries, atomic absorption spectrometry, liquid scintillation counting, radioichromatography • Accelerator Driven Systems for Transmutation of Nuclear Wastes • Determination of actinoids (U, Th, Np, Pu, Am, DU) in biological and environmental matrices, , and spectrometries 13 October 2005 Highligths_Physics 2

Main uses of No Carrier Added Radiotracers 13 October 2005 Highligths_Physics

Production of a N. C. A. radionuclide N. C. A. Labelled compound 13 October 2005 Highligths_Physics

Origins of Isotopic Carrier (both stable and radioactive) 13 October 2005 Highligths_Physics 5

Recent Projects co-funded by INFN Ø RAME-64 (2001 -2002): study of cyclotron production, radiochemical separation and QC of high specific activity copper-64 (copper-61) by deuteron irradiation on natural Zn target Ø ASTATO (2003 -2005): study of cyclotron production of astatine-211 (internally spiked by astatine-210) by alpha irradiation on Bi target. Radiochemical separation and QC. Targetry improvement. Polonium-210 dosimetry ! Ø RENIO (2006– 2007): study of cyclotron production of rhenium-186 g by proton or deuteron irradiation on W 186 target. Radiochemical separation and QC. 13 October 2005 Highligths_Physics 6

Nuclear reactions, main nuclear data and applications of radioisotopes used in nuclear medicine under study Radionuclide T 1/2 reactions gamma emissions imaging radiotherapy 64 Cu 12. 70 h nat. Zn (d, X) gg 511 ke. V PET b+ and b- 61 Cu 3. 33 h nat. Zn (d, X) gg 511 ke. V PET impurity 66 Ga 9. 49 h nat. Zn (d, xn) gg 511 ke. V many gammas PET g-camera b+ , 4. 2 Me. V (p, n) 186 W (d, 2 n) g 137 ke. V other gammas SPET g-camera b- , 1. 1 Me. V 186 W 186 g. Re 89. 25 h 211 At 211 Po 7. 22 h 516 ms 209 Bi ( , 2 n) X 79 ke. V g-camera a , 5. 868 Me. V a , 7. 448 Me. V 210 At 210 Po 8. 3 h 138. 4 d 209 Bi ( , 3 n) many gammas g-camera internal spike a , 5. 304 Me. V 213 Bi 213 Po 10. 0 d 45. 6 m 4. 2 s 226 Ra (p, 2 n) many gammas SPET g-camera a, 5. 829 Me. V, others b- , 1. 4 Me. V a , 8. 375 Me. V 103 Pd 16. 97 d 103 Rh (d, 2 n) X 20, 22, 23 ke. V some gammas --- X 20, 22, 23 ke. V 225 Ac 13 October 2005 Highligths_Physics 7

211 At direct methods Bombarding Bi metallic targets with light ions 209 Bi(t, 209 Bi(a, production methods JRC-Euratom Ispra cyclotron K = 38 Tmax/A = K (Z/A)2 n)211 At I up to 60 A 2 n)211 At indirect methods d up to 19 Me. V p , up to 38 Me. V Beam line Irradiation chamber From the decay of its precursor 211 Rn 209 Bi(6 Li, 4 n) 211 Rn ® 211 At 232 Th(p, spall) 211 Rn ® 211 At 232 Th(g, spall) 211 Rn ® 211 At 13 October 2005 Highligths_Physics 8

Decay scheme of 211 At 211 m. Po 211 At 25, 2 s e 99, 825 % 211 g. Po 207 Pb stabile Reaction ES(Me. V) T 1/2 209 Bi( , 2 n)211 At 20, 72 7, 214 h 209 Bi( , 3 n)210 At 28, 61 8, 1 h 23, 76 138, 376 d 15, 11 138, 376 d 21, 49 138, 376 d 2 n)210 Po 209 Bi( , t)210 Po 13 October 2005 n)210 Po 138, 376 d 0, 175 % (on 206 Bi) Ea=5, 3 Me. V a 100 % (on 206 Pb) a 100 % Ea=7. 5 Me. V e 100 % 209 Bi( , d 210 Po 516 ms 210 At 8, 1 h t e 58, 2 % 31, 55 a 209 Bi( , p 210 A 7. 214 h a 41, 8 % Ea=5. 9 Me. V 207 Bi Decay scheme of ØThe energy of the alpha particles range from 4992 ke. V to 7451 ke. V with an “average “ value of 6. 22 Me. V. ØThe particles of the 211 At/211 g. Po have an “average” range of 60 m in water (and soft animal tissues), and a nearly optimal LET of 130 e. V·nm-1, which is around the maximum of Q curve for energetic ions. ØThe 207 Bi is produced in negligible ammount. ØThe atatine is an alogen: chemistry for labelling molecules is similar to that for iodine. Highligths_Physics

• Radiochemical separations • Nuclear measurements ( , b, g spectrometry) 1. Dissoluzione del irraggiato target Dissoluzione del Bi in HNO 3 concentrato Aggiunta alla soluzione di HCl 8 M 2. Estrazione liquido/liquido Estrazione in solvente organico etere diisopropilico (o tetracloruro di carbonio) Fase organica astato-210, 211 Lavaggio con HCl 8 M 3. Ri-estrazione in fase acquosa Resa: 98 % Fase acquosa polonio-210 e Bi Ri-estrazione con etere diisopropilico Highligths_Physics Resa: 50 % In alternativa riduzione in forma anionica dell’astato in soluzione basica (Na. OH) 13 October 2005 Riduzione in forma anionica dell’astato con agente riducente (cloruro di idrossilammonio) Resa: 90 % 10

HPGe g spectrum – 28. 8 Me. V irradiation 13 October 2005 Highligths_Physics

alpha spectrum after the liquid/liquid extraction: the peaks of both 211 At-211 g. Po and 210 Po are shown together (related to 32. 8 Me. V irradiation). alpha spectrum of the astatine fraction (extracted by the organic solvent): At product is completely extracted from the aqueous solution. alpha spectrum of the separated 210 Po fraction (remained in the aqueous phase): none of the 210 Po is taken into the organic solvent extraction. 13 October 2005 Highligths_Physics

210 At 211 At 209 Bi( , 2 n)211 At 13 October 2005 209 Bi( , Highligths_Physics 3 n)210 At

Production of 186 Re via (p, n) reaction on 186 W target 13 October 2005 Highligths_Physics

Nuclear Physics Laboratory: 4 HPGe connected to 4 MCAs 13 October 2005 Highligths_Physics

Nuclear Physics Laboratory: Na. I(Tl), spectrometer, Geiger-Müller 13 October 2005 Liquid Scintillation Counting Highligths_Physics

Cold Chemistry Laboratory for trace analysis UV-VIS spectrophotometry, polarography-SV, ET-AAS radio-TLC, radio-PC radio-HPLC, radio-GC 13 October 2005 Highligths_Physics

Warm Radiochemistry Laboratory: Class II 13 October 2005 Highligths_Physics

Warm Radiochemistry Laboratory: Class II 13 October 2005 Highligths_Physics

Hot Radiochemistry Laboratory: Class II 13 October 2005 Highligths_Physics

Main Collaboarations with Research Centres • Institute for Health and Consumer Protection, JRCIspra, CE, Varese • Centro Radiochimica/Spettroscopia, CNR, Pavia • ENEA- Centri di Bologna, Saluggia • Dipartimento Scienze Ambientali e Scienze Materiali, Milano-Bicocca • Intitute for Nuclear Research, INR, Troitsk, Moskow Region, Russia • Los Alamos National Laboratory, USA • Ben Gurion University of Be’er Sheva, Israel 13 October 2005 Highligths_Physics 21

Main Collaborations with Hospital Institutions • Istituto Europeo di Oncologia, IEO Servizio Radioterapia e Medicina Nucleare, Milano • Ospedale San Paolo, Servizio Medicina Nucleare, Milano • Ospedali Riuniti di Bergamo, Servizi Medicina Nucleare e Fisica Sanitaria, Bergamo • Ospedale Maggiore-Policlinico, Laboratorio Ciclotrone, Milano • Ospedale Niguarda Ca’ Granda, Servizio Fisica Sanitaria, Milano • Istituto Tumori, Milano 13 October 2005 Highligths_Physics

Laboratorio LASA-Segrate Mauro. Bonardi@mi. infn. it Flavia. Groppi@mi. infn. it Tel: 02 503 19 500 Dipartimento di Fisica – INFN Sezione di Milano Via Fratelli Cervi, 201 – 20090 Segrate (MI) 13 October 2005 Highligths_Physics

Theoretical SA(CF) : SA(CF) = Na / a. m. Specific Activity, SA : SA = Activity of a RN / mass isotopic carrier Isotopic Carrier : total number of atoms “isotopic” with main Radio-Nuclide (both radioactive and stable) Isotopic Dilution Factor : IDF = total number of isotopic atoms divided number of atoms of RN 13 October 2005 Highligths_Physics