NRC-8, EuCheMS International Conference on Nuclear and Radiochemistry

ORAL PRESENTATION - Production of Four Terbium Radioisotopes for Radiopharmaceutical Applications

17 Sept 2012, 15:55

15m

Como, Italy

Oral Communications Radiopharmaceutical chemistry, radiodiagnostics, radiotherapy, theragnostics Session 2 (cn't of Session 1) - Radiopharmaceutical Chemistry (radiodiagnostics, radiotherapy, theragnostics)

Speaker

Mr Holger Dorrer (Paul Scherrer Institut, Villigen-PSI, Switzerland & University of Bern, Berne, Switzerland)

Description

Introduction: Terbium provides 4 radioisotopes, which are suitable for different diagnostic or therapeutic applications in nuclear medicine. These are ¹⁴⁹Tb (T_½ 4.1 h, E_α 3.97 MeV, I_α 16.7 %) for α–radionuclide therapy, ¹⁵²Tb (T_½ 17.5 h, E_β+_,av 1.08 MeV, I_β+ 17 %) for PET, ¹⁵⁵Tb (T_½ 5.3 d, E_γ 86.6/105 keV) for SPECT and ¹⁶¹Tb (T_½ 6.9 d, E_β-_,av 0.154 MeV) for β^--radionuclide therapy. ¹⁶¹Tb is similar to the clinically employed radiolanthanide ¹⁷⁷Lu, but emits in addition a number of conversion- and Auger-electrons. Aim: The production of the four radionuclides should be established in a quality, which is suitable for radiolabeling of biomolecules. Method: Neutron-deficient ¹⁴⁹Tb, ¹⁵²Tb, and ¹⁵⁵Tb were produced at ISOLDE(CERN) by spallation reactions using 1.4 GeV protons onto a 50 g/cm² thick tantalum target followed by online mass separation and deposition onto carrier foils. ¹⁶¹Tb was obtained from neutron irradiation of highly enriched ¹⁶⁰Gd targets at the high flux reactor of ILL, Grenoble or spallation neutron source SINQ, PSI. Chemical separation of Tb radioisotopes was accomplished by cation exchange chromatography using the complexing agent α-hydroxyiso-butyric acid (α-HIBA). Results: 6 MBq ¹⁴⁹Tb, 18 MBq ¹⁵²Tb and 9 MBq ¹⁵⁵Tb were obtained in ≤ 1 mL 0.15 M α-hydroxyisobutyrate solution. Up to 10 GBq ¹⁶¹Tb were produced from irradiated ¹⁶⁰Gd targets and obtained in 300 μL 0.05 M HCl. Radiolabeling of a novel DOTA-folate conjugate was performed with > 96 % yield at Tb:DOTA-folate molar ratios 1:~59000 (¹⁴⁹Tb), 1:~5500 (¹⁵²Tb), 1:~700 (¹⁵⁵Tb) and 1:17 (¹⁶¹Tb). Radiolabeling of DOTATATE was performed with > 99 % yield at ¹⁶¹Tb:DOTA-Tyr³-octreotate molar ratios ≥ 1:6. Conclusion: Successful production of the Tb-radioisotopes enabled synthesis of radiolabeled DOTA-folate conjugates and their evaluation in an in vivo study. Test radiolabeling of DOTATATE confirmed the high specific activity of the obtained ¹⁶¹Tb.