title: Future prospects for SPECT imaging using the radiolanthanide terbium-155 - production and preclinical evaluation in tumor-bearing mice.
abstract: BACKGROUND
  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.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Müller
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Eliane
authors.initials: E
authors.lastname: Fischer
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Behe
authors.affiliation: Institut Laue-Langevin, Grenoble, France.
authors.forename: Ulli
authors.initials: U
authors.lastname: Köster
authors.affiliation: 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.
authors.forename: Holger
authors.initials: H
authors.lastname: Dorrer
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Josefine
authors.initials: J
authors.lastname: Reber
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Haller
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Susan
authors.initials: S
authors.lastname: Cohrs
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Blanc
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Grünberg
authors.affiliation: 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.
authors.forename: Maruta
authors.initials: M
authors.lastname: Bunka
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Zhernosekov
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Nicholas
authors.initials: N
authors.lastname: van der Meulen
authors.affiliation: Physics Department, ISOLDE/CERN, Geneva, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Johnston
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
authors.affiliation: 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.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
mesh_terms: D000818:Animals; D005260:Female; D006207:Half-Life; D006801:Humans; D007624:KB Cells; D051379:Mice; D015282:Octreotide / Q000737:chemistry; D011854:Radiochemistry; D011868:Radioisotopes; D013725:Terbium / Q000737:chemistry* / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: D011868:Radioisotopes; D013725:Terbium; D015282:Octreotide
keywords: Anti-L1-CAM antibody; DOTATATE; Folate; Minigastrin; SPECT; Tb-155