Despite recent technological advancements in microcomputed tomography (micro-CT) and contrast agent development, preclinical contrast agents are still predominantly iodine-based. Higher contrast can be achieved when using elements with higher atomic numbers, such as lanthanides; lanthanides also have X-ray attenuation properties that are ideal for spectral CT. However, the formulation of lanthanide-based contrast agents at the high concentrations required for vascular imaging presents a significant challenge. In this work, we developed an erbium-based contrast agent that meets micro-CT imaging requirements, which include colloidal stability upon redispersion at high concentrations, evasion of rapid renal clearance, and circulation times of tens of minutes in small animals. Through systematic studies with poly(ethylene glycol) (PEG)-poly(propylene glycol), PEG-polycaprolactone, and PEG-poly(l-lactide) (PLA) block copolymers, the amphiphilic block copolymer PEG₁₁₄-PLA₅₃ was identified to be ideal for encapsulating oleate-coated lanthanide-based nanoparticles for in vivo intravenous administration. We were able to synthesize a contrast agent containing 100 mg/mL of erbium that could be redispersed into colloidally stable particles in saline after lyophilization. Contrast enhancement of over 250 HU was achieved in the blood pool for up to an hour, thereby meeting the requirements of live animal micro-CT.

中文翻译：

---

镧系元素纳米粒子的聚合物组装封装作为体内微CT的对比剂

尽管最近在微计算机断层扫描（micro-CT）和造影剂开发方面取得了技术进步，但临床前造影剂仍主要基于碘。当使用原子序数更高的元素（例如镧系元素）时，可以实现更高的对比度。镧系元素还具有X射线衰减特性，非常适合光谱CT。然而，血管成像所需的高浓度的基于镧系元素的造影剂的配制提出了重大挑战。在这项工作中，我们开发了一种满足micro-CT成像要求的基于的造影剂，其中包括在高浓度下重新分散后的胶体稳定性，避免快速清除肾脏以及在小动物中循环数十分钟的时间。1-丙交酯（PLA）嵌段共聚物，两亲性嵌段共聚物PEG ₁₁₄ -PLA ₅₃被确定为封装用于体内静脉内施用的油酸酯包被的镧系元素基纳米颗粒的理想选择。我们能够合成包含100 mg / mL of的造影剂，冷冻干燥后，该造影剂可以重新分散在盐水中的胶体稳定颗粒中。在长达一个小时的时间内，血池中对比度提高了250 HU以上，从而满足了活体微型CT的要求。