Gerd-J. Beyer gerd.beyer@cern.ch

1. Radiochemistry in combination with mass separation Gerd-J. Beyer gerd.beyer@cern.ch MEDICIS Radiochemistry Day March. 19, 20019, CERN

2. Mass separation in combination with high energy p-beam 1970

3. Why metallic radionuclides? • 131I cannot fulfill all requirements (weak in vivo stability) • We learnt to make bio-conjugates, that contain chelating groups • Universality: the chelated bio-conjugates can be labelled practically with any metallic radionuclide of group III and group IV elements • The radiolabeled bio-conjugates are stable in vivo • The bio-selective ligands are mainly monoclonal antibodies or peptides Most important: Rare Earth Elements Why?

4. Why Radio-Lanthanides? The group of rare earth elements contains a complete range of radioisotopes having as complete a diversity of * types of radiation and * energy of radiation and * half life one would wish. SPECT 155Tb,157Dy,167Tm, 169Yb, PET 134Ce/La, 140Nd/Pr, 142Sm/Pm, 152Tb, 86Y ß- (for therapy) 153Sm, 166Ho, 169Er, 177Lu, 90Y, 47Sc Auger-e (140Nd), 165Er, (169Yb) a- 149Tb, 225Ac (213Bi) g for research 139,141Ce 145Sm 153Gd 159Dy 172Lu

5. Why Radio-Lanthanides? • ADANTAGES: CHEMICAL SIMILARITY • systematic studies of biokinetic behaviour without changing the basic molecule • All decay modes, half-life’s available • DISADVANTAGES: CHEMICAL SIMILARITY • difficult separation techniques • impurity problems HOWEVER: The interest (physics, technique) in this exotic group of elements stimulated the development of - Chromatographic separation techniques - Fast radiochemical separation techniques - High purity REE materials

6. Radiolanthanides at spallation or fission 1 or 1.4 GeV protons pulsed beam, 3 1013 p/pulse (~1µA) Ta-foil- or U-carbide target Surface ionization ion source 122 g/cm2 Ta (rolls of 25 µm foils) at 2400 oC W-tube as ionizer at 2800oC Radioactive Ion Beams of 40 elements possible today mass number 148 149 150 151 152 Plasma Ion Source Surface Ionization Target Ion Source

7. DUBNA 1968

8. Radiochemical Separation techniques useful for obtaining radiolanthanides in high purity Cementation with Na-Amalgam Anion-exchange chromatography Reduction-Oxidation Extraction Electro-precipitation Gaschromatography Vacuum-Thermochromatography On line isotope separation technique

9. Chromatographic Separation Influence of Carrier: Carrier free  symmetric elution prophile Macroscopic  assymmetric prophile

10. Separation of carrier-free radiolanthanides from Lanthanide targets: Extraction Chromatography Column: 100 g Silicagel , 26 x 410 mm 0.6 g HDEHP / g silicagel Elution: 2.68 M HCl, 7 ml/min, 40 oC Column: Silicagel , 2.2 x 66 mm 0.6 g HDEHP / g silicagel Elution: 0.97 M HCl, 0.2 ml/min 149Gd 1 carrierfree 2 0.10 mg 3 0.25 mg 4 0.60 mg 5 1.0 mg 6 1.5 mg 7 2.5 mg (= 20 %capacity) 97 74 22 % Eu 2g Er Tb Dy Er concentration in µg/ml / rel.radioactivity concentration Gd-concentratin in µg/fraction Counts per minute Eluted volume / drops 0 10 20 30 40 min E.Herrmann, H.Grosse-Ruyken, V.A.Khalkin J.Chromatog. 87, 351, (1973)

11. Separation of carrier-free radiolanthanides from Lanthanide targets: Scillard Chalmers Effect High purity Lanthanides are irradiated in the chemical form of their DTPA-complexes. The nuclear reaction products are stabilized in cationic form and separated as such in water solution from the target material which remains in the anionic form. One works with 1 g lanthanide target material in the same way as with carrierfree radiolanthanides Column: Dowex 50 x8, 20 µm, NH4+-configuration Elution: a-HIBA, pH=4.7, different concentration 0.15 ml/min Gd (NH4)2[ErDTPA]x 2 H2O (NH4)2[DyDTPA]x 2 H2O (NH4)2[GdDTPA]x 2 H2O G.J.Beyer, H.Grosse-Ruyken et al., J.Inorg.Nucl.Chem., 31 2135 (1969)

12. Separation of high purity radiolanthanides from lanthanide targets by cation exchange chromatography: Two step approach 2. separation 157Tb Column: Aminex A5, NH4+config. 4 x 120 mm, Eluent: 0.155 a-HIBA pH = 4.7 speed 0.15 ml/min Target: 10 mg 156Dy reactor irradiated a-HIBA 1 M 157 158 159 139LaO+ 1. separation mass spectrum 157Tb

13. Thermochromatographic Separation

15. Separation of radiolanthanides from a Hf target by vacuum thermochromatography 800 MeV protons interact with a metallic Hf generating all radio-lanthanides. The radiolanthanides can be released from Hf very fast (within seconds) at T = 2000 oC. The radiolanthanides are than deposited along the Ta-tube according to their individual adsorption enthalpies. The whole process took 5 minutes. Heat screen Hf-target cathode Mo-crucible Ta-tube G.Beyer, A.F.Novgorodov, F.Rösch, H.L.Ravn, Isotopenpraxis 25, 1 (1989)

16. Influence of Carrier in Mass Separation Dubna Surface Ionization Ion Source Uni. Mainz Example Sr: Sr-Mass: 10 µg Sr Ion Current Sr+: 1.0 nA Separation time: ~1.5 h Yield: ~80 %

17. Ion current in nA T = 3000 K Start of automatic furnace Regulation for fixed Ion current I = 1000 nA Separation time in seconds High Purity 82Sr-82Rb Generator 82Sr 82Rb82Kr 25.5 d 76 sec ß+ EC Mo (p,spall) 82,85Sr natRb (p,xn) 82,85Sr (x=4..2) Separation of 1.1*1017 Sr atoms, Total efficiency = 79.9 % Problem: at end of bombardment the content of the “impurity” 85Sr exceeds the “main product” 82Sr by a factor 3 with increasing tendency because of the longer half life. High purity 82Sr would allow to use higher activity load and longer use of the generator. Ionization yield in % e-bombardment heating 2750oC Radiation heating 2000oC Separation yield for 1017 Sr atoms, 2700 oC , 700–1200 nA ion current K.Zimmer, Thesis, University Mainz (Germany) 1995 G.J.Beyer, E.Herrmann, A.Piotrovski et al. NIM 96 (1971) 437-439 G.J.Beyer, F.Rösch, H.L.Ravn “A High Purity 82Sr/82Rb generator CERN-EP/90-91 (29 June 1990) Yu.V.Yushkevich, K.Zimmer, G.J.Beyer et al. JINR-P13-94-213, Dubna, 1994 Ionizer (W) Dubna Surface Ionization Ion Source

18. Long lived Nuclides for R&D Massive components of old ISOLDE Targets Contain valuable radio-lanthanides

20. 225Ac UC-ISOL target, W/surface ionization 225Fr 225Ra 225Ac • A=225 collections gives 225Fr and 225Ra in reasonable yields, (depending on p-energy) • 225Ac groth in within 10 days • 225Ra-225Ac generator: • Cation exchange chromatography on • a mini-AMINEX A5 column is performed, • 225Ac is eluted with 0.8 M a-HIB, while the • 225Ra remains at the column. One week later one can elute another 225Ac preparation and so on. • We ussually collected radiolanthanides in the • same run and performed the deep purification together with the 225Ac. • 4. Due to the lower energy ISAC is most suitable to make reasonable activities of 225Ac.

21. Tomas Diaz de la Rubia Ass.Director of Chemistryand Material SciencesLawrence Livermore National laboratory, in Science and Technology Review July/August 2003 « With so much demand for nuclear chemists and so few university programs supplying them, Livermore must create its own experts. Helping to detect and cure cancer may seem far removed from keeping the nation’s nuclear stockpile safe and secure ….. In fact, the cancer research not only addresses an important national health issue but is also an effective tool for training nuclear chemists to confront national and worldwide security concerns.»