使用放射性镧系元素铽-155进行单光子发射计算机断层扫描（SPECT）成像的未来前景——在荷瘤小鼠中的制备及临床前评估

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

作者信息

Müller Cristina, Fischer Eliane, Behe Martin, Köster Ulli, Dorrer Holger, Reber Josefine, Haller Stephanie, Cohrs Susan, Blanc Alain, Grünberg Jürgen, Bunka Maruta, Zhernosekov Konstantin, van der Meulen Nicholas, Johnston Karl, Türler Andreas, Schibli Roger

机构信息

Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.

Institut Laue-Langevin, Grenoble, France.

出版信息

Nucl Med Biol. 2014 May;41 Suppl:e58-65. doi: 10.1016/j.nucmedbio.2013.11.002. Epub 2013 Nov 15.

DOI:10.1016/j.nucmedbio.2013.11.002

PMID:24360901

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.

摘要

引言

我们使用临床前SPECT成像评估了放射性镧系元素（155）Tb（半衰期t1/2 = 5.32天，Eγ = 87 keV（32%），105 keV（25%））与多种肿瘤靶向生物分子联合使用的适用性。

方法

（155）Tb在瑞士日内瓦欧洲核子研究中心的ISOLDE通过用高能（~1.4 GeV）质子辐照钽靶，随后进行电离和在线质量分离产生。通过阳离子交换色谱法将（155）Tb与同量异位素和假同量异位素杂质分离。四种肿瘤靶向分子——一种生长抑素类似物（DOTATATE）、一种胃泌素小肽类似物（MD）、一种叶酸衍生物（cm09）和一种抗L1-CAM抗体（chCE7）——用（155）Tb进行放射性标记。使用专用的小动物SPECT/CT扫描仪对携带AR42J、表达胆囊收缩素-2受体的A431、KB、IGROV-1和SKOV-3ip肿瘤异种移植的裸鼠进行成像研究。

结果

（155）Tb两步分离过程的总产率为86%。（155）Tb在适合直接标记过程的生理l-乳酸盐溶液中获得。（155）Tb标记的肿瘤靶向生物分子以合理的比活度和高纯度（>95%）获得。（155）Tb给出了高质量、高分辨率的断层图像。SPECT/CT实验分别在注射（155）Tb-DOTATATE和（155）Tb-MD后，出色地显示了小鼠体内的AR42J和表达CCK-2受体的A431肿瘤异种移植。（155）Tb相对较长的物理半衰期特别匹配（155）Tb-cm09和（155）Tb-DTPA-chCE7的生物半衰期，使得即使在给药几天后也能对KB肿瘤、IGROV-1和SKOV-3ip肿瘤进行SPECT成像。