Cristina Müller1, Eliane Fischer1, Martin Behe1, Ulli Köster2, Holger Dorrer3, Josefine Reber1, Stephanie Haller1, Susan Cohrs1, Alain Blanc1, Jürgen Grünberg1, Maruta Bunka3, Konstantin Zhernosekov4, Nicholas van der Meulen4, Karl Johnston5, Andreas Türler3, Roger Schibli6. 1. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland. 2. Institut Laue-Langevin, Grenoble, France. 3. Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland; Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland. 4. Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland. 5. Physics Department, ISOLDE/CERN, Geneva, Switzerland. 6. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland; Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. Electronic address: roger.schibli@psi.ch.
Abstract
INTRODUCTION: We assessed the suitability of the radiolanthanide (155)Tb (t1/2=5.32 days, Eγ=87 keV (32%), 105keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. METHODS: (155)Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (~1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. (155)Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules - a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) - were radiolabeled with (155)Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. RESULTS: The total yield of the two-step separation process of (155)Tb was 86%. (155)Tb was obtained in a physiological l-lactate solution suitable for direct labeling processes. The (155)Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (>95%). (155)Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of (155)Tb-DOTATATE and (155)Tb-MD, respectively. The relatively long physical half-life of (155)Tb matched in particular the biological half-lives of (155)Tb-cm09 and (155)Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. CONCLUSIONS: The radiolanthanide (155)Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β(-)-emitting radiolanthanides (177)Lu, (161)Tb, (166)Ho, and the pseudo-radiolanthanide (90)Y.
INTRODUCTION: We assessed the suitability of the radiolanthanide (155)Tb (t1/2=5.32 days, Eγ=87 keV (32%), 105keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. METHODS: (155)Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (~1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. (155)Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules - a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) - were radiolabeled with (155)Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. RESULTS: The total yield of the two-step separation process of (155)Tb was 86%. (155)Tb was obtained in a physiological l-lactate solution suitable for direct labeling processes. The (155)Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (>95%). (155)Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of (155)Tb-DOTATATE and (155)Tb-MD, respectively. The relatively long physical half-life of (155)Tb matched in particular the biological half-lives of (155)Tb-cm09 and (155)Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. CONCLUSIONS: The radiolanthanide (155)Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β(-)-emitting radiolanthanides (177)Lu, (161)Tb, (166)Ho, and the pseudo-radiolanthanide (90)Y.
Authors: Richard P Baum; Aviral Singh; Harshad R Kulkarni; Peter Bernhardt; Tobias Rydén; Christiane Schuchardt; Nadezda Gracheva; Pascal V Grundler; Ulli Köster; Dirk Müller; Michael Pröhl; Jan Rijn Zeevaart; Roger Schibli; Nicholas P van der Meulen; Cristina Müller Journal: J Nucl Med Date: 2021-02-05 Impact factor: 10.057
Authors: Charlotte Duchemin; Thomas E Cocolios; Kristof Dockx; Gregory J Farooq-Smith; Olaf Felden; Roberto Formento-Cavaier; Ralf Gebel; Ulli Köster; Bernd Neumaier; Bernhard Scholten; Ingo Spahn; Stefan Spellerberg; Maria E Stamati; Simon Stegemann; Hannelore Verhoeven Journal: Front Med (Lausanne) Date: 2021-05-12
Authors: Zeynep Talip; Francesca Borgna; Cristina Müller; Jiri Ulrich; Charlotte Duchemin; Joao P Ramos; Thierry Stora; Ulli Köster; Youcef Nedjadi; Vadim Gadelshin; Valentin N Fedosseev; Frederic Juget; Claude Bailat; Adelheid Fankhauser; Shane G Wilkins; Laura Lambert; Bruce Marsh; Dmitry Fedorov; Eric Chevallay; Pascal Fernier; Roger Schibli; Nicholas P van der Meulen Journal: Front Med (Lausanne) Date: 2021-04-22
Authors: Cristina Müller; Christiaan Vermeulen; Karl Johnston; Ulli Köster; Raffaella Schmid; Andreas Türler; Nicholas P van der Meulen Journal: EJNMMI Res Date: 2016-04-23 Impact factor: 3.138
Authors: Ben Webster; Peter Ivanov; Ben Russell; Sean Collins; Thierry Stora; Joao Pedro Ramos; Ulli Köster; Andrew Paul Robinson; David Read Journal: Sci Rep Date: 2019-07-26 Impact factor: 4.379
Authors: Cristina Müller; Christoph A Umbricht; Nadezda Gracheva; Viviane J Tschan; Giovanni Pellegrini; Peter Bernhardt; Jan Rijn Zeevaart; Ulli Köster; Roger Schibli; Nicholas P van der Meulen Journal: Eur J Nucl Med Mol Imaging Date: 2019-05-27 Impact factor: 9.236