Future prospects for SPECT imaging using the radiolanthanide terbium-155 - production and preclinical evaluation in tumor-bearing mice.

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.

• Authors: Cristina Müller, Eliane Fischer, Martin Behe, Ulli Köster, Holger Dorrer, Josefine Reber, Stephanie Haller, Susan Cohrs, Alain Blanc, Jürgen Grünberg, Maruta Bunka, Konstantin Zhernosekov, Nicholas van der Meulen, Karl Johnston, Andreas Türler, Roger Schibli
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 41 Suppl Pg. e58-65 (May 2014) ISSN: 1872-9614 [Electronic] United States
• PMID: 24360901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Radioisotopes
• Terbium
• Octreotide

Topics

• Animals
• Female
• Half-Life
• Humans
• KB Cells
• Mice
• Octreotide (chemistry)
• Radiochemistry
• Radioisotopes
• Terbium (chemistry, pharmacokinetics)
• Tomography, Emission-Computed, Single-Photon (methods)
• Tomography, X-Ray Computed