Schulz Jörg, Rohracker Martin, Stiebler Marvin, Goldschmidt Jürgen, Grosser Oliver S, Osterkamp Frank, Pethe Annette, Reineke Ulrich, Smerling Christiane, Amthauer Holger
Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany.
Leibniz-Institut für Neurobiologie, Magdeburg, Germany.
J Nucl Med. 2016 Jul;57(7):1120-3. doi: 10.2967/jnumed.115.170530. Epub 2016 Mar 3.
Neurotensin receptor-1 (NTR1) is a promising target for diagnostic imaging and targeted radionuclide therapy. The aim of this study was to evaluate the biodistribution profiles of a series of newly developed diarylpyrazole-based NTR1 antagonists regarding their suitability as diagnostic and potentially radiotherapeutic agents.
3BP-227, 3BP-228, and 3BP-483 were labeled with (111)In and injected intravenously into NTR1-positive HT29 xenograft-bearing nude mice. At 3, 6, 12, and 24 h after administration, SPECT/CT images were acquired or mice were sacrificed for ex vivo determination of tissue-associated radioactivity.
High-contrast tumor visualization in SPECT/CT images was achieved using the 3 compounds of this study. Ex vivo biodistribution studies confirmed a high and persistent tumor uptake, peaking at 6 h after injection for (111)In-3BP-227 (8.4 ± 3.1 percentage injected dose per gram [%ID/g]) and at 3 h after injection for (111)In-3BP-228 (10.2 ± 5.3 %ID/g) and (111)In-3BP-483 (1.9 ± 0.8 %ID/g). Tumor-to-normal-tissue ratios obtained with (111)In-3BP-227 and (111)In-3BP-228 were consistently greater than 1.
On the basis of the superior biodistribution profile compared with previously reported radiolabeled NTR1 ligands, (111)In-3BP-227 is an ideal candidate for further development as a theranostic tracer.
神经降压素受体-1（NTR1）是诊断成像和靶向放射性核素治疗的一个有前景的靶点。本研究的目的是评估一系列新开发的基于二芳基吡唑的NTR1拮抗剂作为诊断和潜在放射治疗剂的生物分布情况。
将3BP-227、3BP-228和3BP-483用（111）铟标记，静脉注射到携带NTR1阳性HT29异种移植瘤的裸鼠体内。给药后3、6、12和24小时，采集SPECT/CT图像，或处死小鼠以进行组织相关放射性的离体测定。
使用本研究的3种化合物在SPECT/CT图像中实现了高对比度的肿瘤可视化。离体生物分布研究证实肿瘤摄取高且持续，（111）铟-3BP-227在注射后6小时达到峰值（8.4±3.1每克注射剂量百分比[%ID/g]），（111）铟-3BP-228和（111）铟-3BP-483在注射后3小时达到峰值（分别为10.2±5.3 %ID/g和1.9±0.8 %ID/g）。（111）铟-3BP-227和（111）铟-3BP-228获得的肿瘤与正常组织的比值始终大于1。
基于与先前报道的放射性标记的NTR1配体相比更优的生物分布情况，（111）铟-3BP-227是作为治疗诊断示踪剂进一步开发的理想候选物。
