Microchip electrophoresis as basis for fully integrated, fully automated, low-cost radiopharmaceutical QC platform
微芯片电泳作为完全集成、全自动、低成本放射性药物 QC 平台的基础
基本信息
- 批准号:10697506
- 负责人:
- 金额:$ 27.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAliquotAminesAnimalsAreaAutomationBiological AssayBlood capillariesCalibrationCapillary ElectrophoresisCellsChargeChemicalsClinicalComplexConsumptionDetectionDevelopmentDevicesDiagnostic ImagingDoseEnsureEquipmentFOLH1 geneFormulationGeometryGoldHeadHigh Pressure Liquid ChromatographyHumanHuman ResourcesInfrastructureIsotopesLabelLaboratoriesMeasurementMeasuresMedicineMethodsMicrochip ElectrophoresisMicrofluidicsMiniaturizationMolecularMonitorNatureOpticsOutcomePatientsPerformancePhasePlayPositron-Emission TomographyProcessProductionPublishingQuality ControlRadiationRadioRadiochemistryRadioisotopesRadiopharmaceuticalsReagentReportingResearchResolutionRoleSafetySamplingSilicon DioxideSourceSpecificitySystemTechnetium 99mTechniquesTechnologyTestingTherapeuticTimeTracerValidationWorkclinical carecommercial prototypecostdetection sensitivitydetectordrug developmentimaging agentimprovedin vivoinstrumentinstrumentationmanufactureoperationpatient safetypre-clinicalradiochemicalradiotracerskillstool
项目摘要
PROJECT SUMMARY
Positron emission tomography (PET) is an indispensable tool in research, drug development and clinical care,
due to its very high sensitivity and quantitative nature. The complexity and high cost of producing PET tracers
limits their use in research and their development and validation into quantitative in vivo biological assays. For
example, thousands of different PET tracers have been reported, but very few have been validated for use in
animals or humans, and only a tiny fraction are approved for routine use in patients.
New methods being developed for PET tracer manufacturing – especially microfluidics – have demonstrated
potential for vastly reduced tracer production cost and complexity through (i) reduction of expensive reagents,
(ii) efficient production at preclinical and clinical scales, and (iii) compact instrumentation that can be operated
with minimal infrastructure. As the quality control (QC) tests necessary to ensure radiopharmaceutical safety
must be performed after every synthesis, there have been some efforts to apply microfluidics in this area as
well. DropletPharm, Inc. seeks to leverage microfluidic developments to create a tabletop radiopharmacy
platform to eliminate the typical costly radiopharmacy infrastructure (i.e. hot cell, radiosynthesizer, stack
monitoring system, QC equipment), and replace it with a self-shielded benchtop device that performs both
synthesis and analysis. In the current project, we seek to develop a microfluidics-based QC platform to
automatically perform all necessary radiopharmaceutical QC tests, reducing costs and increasing throughput.
While many QC tests can be implemented as simple optical and radiation measurements (of aliquots
pre-mixed with indicators), the (radio)chemical identity and purity tests are more challenging and require
chemical separations. Recently, numerous research groups have used capillary electrophoresis for rapid
separation and analysis of radiopharmaceuticals labeled with various isotopes (incl. Tc-99m and F-18). The
van Dam lab used [18F]FLT samples to demonstrate high-resolution and sensitivity can be achieved using
microchip electrophoresis (MCE), where advantages of vastly reduced size, lower cost, and short analysis time
makes this technique highly attractive as a replacement for the gold standard techniques of radio-HPLC or
radio-TLC for assessing radiochemical identity and purity as well as chemical purity and molar activity. To
assess the technical feasibility to use this technology at the core of DropletPharm’s QC testing platform, this
proposal aims to address two limitations of the method published to date, and compare the analysis
performance head-to-head with radio-HPLC or radio-TLC. Aim 1 will explore strategies to improve radiation
detection sensitivity to enable the analysis of a wider range of clinical batches (i.e. those that are more dilute).
Aim 2 will explore radio-MCE separation of example radiotracers, including [18F]FLT and [68Ga]Ga-PSMA-11,
and compare performance with the gold standard (radio-HPLC and radio-TLC). Successful completion of the
milestones will indicate that Phase II commercial development into a full QC-testing module is warranted.
项目总结
正电子发射断层扫描(PET)是研究、药物开发和临床护理中不可或缺的工具,
由于它具有很高的灵敏度和量化性质。生产PET示踪剂的复杂性和高成本
限制了它们在研究中的使用,以及它们在体内生物定量检测中的开发和验证。为
例如,已经报道了数千种不同的PET示踪剂,但很少有被验证用于
动物或人类,只有一小部分被批准用于患者的常规使用。
正在开发的制造PET示踪剂的新方法--特别是微流体--已经证明
通过(I)减少昂贵的试剂,极大地降低示踪剂生产成本和复杂性的潜力,
(2)临床前和临床规模的高效生产;和(3)可操作的紧凑型仪器
只需最少的基础设施。作为确保放射性药物安全所必需的质量控制(QC)测试
必须在每次合成后进行,已经有一些努力在这一领域应用微流控技术,如
井。DropletPharm公司寻求利用微流控技术的发展来创造一种桌面放射性药物
消除典型的昂贵的放射性药学基础设施(即热室、放射性合成器、堆栈)的平台
监控系统、QC设备),并用可同时执行以下两种功能的自屏蔽台式设备来取代
综合和分析。在目前的项目中,我们试图开发一个基于微流控的QC平台来
自动执行所有必要的放射性药物QC测试,从而降低成本并提高产量。
虽然许多质量控制测试可以实施为简单的光学和辐射测量(等分的
预混有指示剂),(无线电)化学特性和纯度测试更具挑战性和要求
化学分离。最近,许多研究小组使用毛细管电泳法进行快速检测
各种同位素标记的放射性药物的分离和分析。TC-99M和F-18)。这个
Van Dam实验室使用[18F]FLT样本演示了使用
微芯片电泳(MCE),具有体积小、成本低、分析时间短等优点
使这项技术非常有吸引力,作为替代放射-高效液相或
放射-薄层色谱用于评估放射化学特性和纯度以及化学纯度和摩尔活度。至
评估在DropletPharm的QC测试平台的核心使用该技术的技术可行性
该提案旨在解决迄今为止发表的方法的两个局限性,并将分析结果进行比较
通过无线电-高效液相色谱或无线电-薄层色谱进行面对面的性能分析。目标1将探索改善辐射的策略
检测灵敏度,以实现对更大范围的临床批次(即那些更稀释的批次)的分析。
目标2将探索示例放射性示踪剂的无线电-MCE分离,包括[18F]Flt和[68Ga]Ga-PSMA-11,
并与金标准(RADIO-HPL C和RADIO-TLC)进行性能比较。圆满完成
里程碑将表明,第二阶段商业开发成为完整的质量控制测试模块是有保证的。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jason Jones其他文献
Jason Jones的其他文献
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{{ truncateString('Jason Jones', 18)}}的其他基金
Demonstrating miniaturized production of a KOR PET tracer as a proof-of-concept for low-cost distribution of nascent PET neurotracers
展示 KOR PET 示踪剂的小型化生产,作为新兴 PET 神经示踪剂低成本分销的概念验证
- 批准号:
10822523 - 财政年份:2023
- 资助金额:
$ 27.58万 - 项目类别:
Production of radiometal-based radiopharmaceuticals at a clinical scale via droplet-scale radiochemistry
通过液滴规模放射化学在临床规模生产基于放射性金属的放射性药物
- 批准号:
10697509 - 财政年份:2023
- 资助金额:
$ 27.58万 - 项目类别:
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