Microfluidic systems for high efficiency radiolabeling and purification of nanomedicines

用于纳米药物高效放射性标记和纯化的微流体系统

• 批准号: RGPIN-2018-04958
• 负责人: Hafeli, Urs
• 金额: $ 2.04万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=652801
• 关键词: Microfluidic; systems; efficiency; radiolabeling; purification

One method of investigating disease pathways or diagnosing diseases is imaging using single photon emission computed tomography (SPECT). With SPECT, a gamma-emitting radioisotope is connected to or incorporated into a molecule, a macromolecular compound, or a compound in the nano- to micro-meter range. Most often, this radiolabeling step is accomplished using a kit format, where the radioactivity is added to a vial of all the other ingredients to quickly obtain the radiolabeled compound and this compound is then injected into an animal or patient. The kit format, however, cannot always be used, as the introduction of the radioisotope might change the properties of the final radiolabeled compound, or the chemistry of the system might not allow for an efficient radiolabeling procedure (multiple steps required, radiation hazard, air sensitive, separation steps needed). ***This project aims to build a microfluidics micro-/nanodevice to overcome difficulties of radiolabeling and purifying radiopharmaceuticals that include nanoparticles, microspheres, and macromolecular compounds. We will carefully integrate the radiolabeling step inside microfluidic channels, which will be optimized for diffusion and reaction kinetics. We will also, if necessary, apply forced mixing on built-in mixing structures, use a built-in heatable reactor feature, and concentrate and separate the resulting compounds and nanomedicines with microfluidic Dean forces, based on our recent research in this field. An additional separation feature might be the use of local magnetic forces. The aim is to improve on the ease of procedure and the radiolabeling efficiency, while at the same time allowing for ideally aseptic conditions and ease of quality control. The resulting radiopharmaceuticals will be compared to the conventional techniques in terms of material use (which is hypothesized to be much less), reaction time (likely shorter), and radiolabeling efficiency (likely higher). Different radioisotope systems will be investigated, with rhenium-based ones (for example Re-188) being at the forefront. Currently, their oxidation sensitivity (back to water soluble perrhenate) is a problem, and will be optimized for future therapeutic applications. Microfluidic based methods for the preparation of diagnostic and therapeutic radiopharmaceuticals might thus be crucial to allow for high enough radiation concentrations, and provide truly theranostic agents for future detection and treatment of cancer.

一种研究疾病途径或诊断疾病的方法是使用单个光子发射计算机断层扫描（SPECT）进行成像。使用SPECT，将γ发射放射性同位素连接到分子，大分子化合物或纳米至微米范围的化合物中。最常见的是，使用套件格式完成此放射性标记的步骤，其中放射性被添加到所有其他成分的小瓶中，以快速获得放射性标记的化合物，然后将该化合物注入动物或患者。然而，套件格式不能总是使用，因为放射性同位素的引入可能会更改最终放射性标记化合物的性质，或者系统的化学性质可能不允许进行有效的放射性标记程序（所需的多个辐射危险，空气敏感的，敏感的，分离步骤，所需的分离步骤）。 ***该项目旨在构建微流体微流体/纳米电视，以克服放射性标记和净化放射性药物的困难，包括纳米颗粒，微球和大分子化合物。我们将仔细整合微流体通道内的放射性标记步骤，该步骤将优化用于扩散和反应动力学。根据我们在该领域的最新研究，我们还将在内置混合结构上使用强制混合，使用内置的加热反应器特征，并使用微流体院长力量和将所得化合物和纳米医学分开。另一个分离特征可能是使用局部磁力。目的是提高程序的易度性和放射标记效率，同时允许理想的无菌条件和质量控制易用性。将所得的放射性药物与材料使用（假设要少得多），反应时间（可能更短）和放射性映射效率（可能更高）（可能更高）的传统技术进行比较。将研究不同的放射性同位素系统，基于Rhenium的系统（例如RE-188）处于最前沿。当前，它们的氧化敏感性（回到水溶性perrhenate）是一个问题，将针对将来的治疗应用进行优化。因此，基于微流体的方法用于制备诊断和治疗性放射性药物可能对允许足够高的辐射浓度至关重要，并为未来的检测和治疗癌症提供真正的疗法剂。