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

Müller, Cristina; Fischer, Eliane; Behe, Martin; Köster, Ulli; Dorrer, Holger Johann; Reber, Josefine; Haller, Stephanie; Cohrs, Susan; Blanc, Alain; Grünberg, Jürgen; Bunka, Maruta; Zhernosekov, Konstantin; van der Meulen, Nicholas; Johnston, Karl; Türler, Andreas; Schibli, Roger (2014). Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice. Nuclear medicine and biology, 41 Suppl, e58-65. Elsevier 10.1016/j.nucmedbio.2013.11.002

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We assessed the suitability of the radiolanthanide 155 Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging.
Methods

155Tb 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 177Lu, 161 Tb, 166Ho, and the pseudo-radiolanthanide 90Y.

Item Type:	Journal Article (Original Article)
Division/Institute:	08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
UniBE Contributor:	Dorrer, Holger Johann, Bunka, Maruta, Türler, Andreas
Subjects:	500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry
ISSN:	0969-8051
Publisher:	Elsevier
Language:	English
Submitter:	Franziska Bornhauser-Rufer
Date Deposited:	04 Apr 2014 21:16
Last Modified:	05 Dec 2022 14:31
Publisher DOI:	10.1016/j.nucmedbio.2013.11.002
PubMed ID:	24360901
URI:	https://boris.unibe.ch/id/eprint/46410