Stephens Ross W, Tredwell Gregory D, Bell Jessica L, Knox Karen J, Philip Lee A, Senden Tim J, Tapner Michael J, Bickley Stephanie A, Tanudji Marcel R, Jones Stephen K
The Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics, Australian National University, Canberra, ACT, Australia.
Sirtex Medical Ltd, Sydney, Australia.
Biomater Res. 2021 Mar 31;25(1):7. doi: 10.1186/s40824-021-00210-0.
Understanding the regional vascular delivery of particles to tumour sites is a prerequisite for developing new diagnostic and therapeutic composites for treatment of oncology patients. We describe a novel imageable Ga-radiolabelled polymer composite that is biocompatible in an animal tumour model and can be used for preclinical imaging investigations of the transit of different sized particles through arterial networks of normal and tumour-bearing organs.
Radiolabelling of polymer microspheres with Ga was achieved using a simple mix and wash method, with tannic acid as an immobilising agent. Final in vitro binding yields after autoclaving averaged 94.7%. In vivo stability of the composite was demonstrated in New Zealand white rabbits by intravenous administration, and intrahepatic artery instillations were made in normal and VX2 tumour implanted rabbit livers. Stability of radiolabel was sufficient for rabbit lung and liver imaging over at least 3 hours and 1 hour respectively, with lung retention of radiolabel over 91%, and retention in both normal and VX2 implanted livers of over 95%. SPECT-CT imaging of anaesthetised animals and planar imaging of excised livers showed visible accumulation of radiolabel in tumours. Importantly, microsphere administration and complete liver dispersal was more easily achieved with 8 μm diameter MS than with 30 μm MS, and the smaller microspheres provided more distinct and localised tumour imaging.
This method of producing Ga-radiolabelled polymer microspheres is suitable for SPECT-CT imaging of the regional vascular delivery of microspheres to tumour sites in animal models. Sharper distinction of model tumours from normal liver was obtained with smaller MS, and tumour resolution may be further improved by the use of Ga instead of Ga, to enable PET imaging.
了解颗粒在肿瘤部位的区域血管输送情况是开发用于治疗肿瘤患者的新型诊断和治疗复合材料的前提条件。我们描述了一种新型的可成像的镓标记聚合物复合材料，该材料在动物肿瘤模型中具有生物相容性，可用于临床前成像研究不同大小的颗粒通过正常器官和荷瘤器官动脉网络的转运情况。
使用简单的混合和洗涤方法，以单宁酸作为固定剂，实现了聚合物微球与镓的放射性标记。高压灭菌后的最终体外结合产率平均为94.7%。通过静脉注射在新西兰白兔体内证明了复合材料的体内稳定性，并在正常和VX2肿瘤植入的兔肝脏中进行了肝动脉灌注。放射性标记的稳定性足以分别在至少3小时和1小时内对兔肺和肝脏进行成像，肺部放射性标记保留率超过91%，正常肝脏和VX2植入肝脏中的保留率均超过95%。对麻醉动物的SPECT-CT成像和切除肝脏的平面成像显示肿瘤中有明显的放射性标记积累。重要的是，与30μm的微球相比，直径8μm的微球更容易实现微球给药和肝脏完全分散，并且较小的微球提供了更清晰和局部化的肿瘤成像。
这种生产镓标记聚合物微球的方法适用于在动物模型中对微球向肿瘤部位的区域血管输送进行SPECT-CT成像。使用较小的微球可以更清晰地区分模型肿瘤与正常肝脏，并且通过使用镓代替镓以实现PET成像，可能会进一步提高肿瘤分辨率。
