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 radiolanthanide155 Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. Methods155 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 with155 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 of155 Tb was 86%.155 Tb was obtained in a physiological l -lactate solution suitable for direct labeling processes. The155 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 of155 Tb-DOTATATE and155 Tb-MD, respectively. The relatively long physical half-life of155 Tb matched in particular the biological half-lives of155 Tb-cm09 and155 Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. Conclusions The radiolanthanide155 Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β- -emitting radiolanthanides177 Lu,161 Tb,166 Ho, and the pseudo-radiolanthanide90 Y.