Purpose

Current PET radiotracer production models result in facility and operational costs that scale prohibitively with the number of tracers synthesized, particularly those made as a single dose-on-demand. Short of a paradigm shift in the technology and economics of radiotracer production, the impact of PET on precision medicine will be limited. Inexpensive, microfluidic radiochemistry platforms have the potential to significantly reduce costs associated with dose-on-demand production and expand the breadth of PET tracers accessible for molecular imaging.

Procedures

To produce a miniaturized dose-on-demand device for [⁶⁸Ga]Ga-PSMA-11 production, a microfluidic chip was assembled in polydimethylsiloxane (PDMS), combining all components of tracer production in an integrated, compact, and easily utilized platform. On-chip radionuclide concentration, as well as radionuclide and precursor starting material mixing and reaction were incorporated. The radionuclide was sourced from a standard, commercially available ⁶⁸Ge/⁶⁸Ga generator. Optimal reaction conditions were determined, which included precursor concentration (5 μg/mL), temperature (95 °C), and reaction time (1 min).

Results

The total trapping efficiency of combined on-chip SCX and SAX columns was greater than 70 % and could be accomplished in ~ 12 min. Under optimized conditions, [⁶⁸Ga]Ga-PSMA-11 could be reliably synthesized starting from a complete generator elution (1100 MBq [29.7 mCi]) in ~ 12 min, with an average radiochemical yield of 70 %, radiochemical purity > 99 %, and specific activity > 740 MBq/μg (20 mCi/μg). Quality control testing demonstrated that tracer produced using this platform met or exceeded all typical FDA requirements for human use.

Conclusions

A simple, low-cost, dose-on-demand radiosynthesis strategy, such as the chip presented here, represents an opportunity to reduce the financial barriers associated with PET imaging. While this study focused on a device for [⁶⁸Ga]Ga-PSMA-11, the technology is also applicable to a wide range of other tracers where low-cost, automated, dose-on-demand production is highly desirable.

中文翻译：

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使用低成本微流体装置对 [68Ga]Ga-PSMA-11 进行高产放射合成。

目的

当前的 PET 放射性示踪剂生产模型导致设施和运营成本随着合成示踪剂的数量而大幅增加，特别是那些按需单剂量制造的示踪剂。缺乏放射性示踪剂生产技术和经济性的范式转变，PET 对精准医学的影响将是有限的。廉价的微流体放射化学平台有可能显着降低与按需剂量生产相关的成本，并扩大可用于分子成像的 PET 示踪剂的广度。

程序

^{为了生产用于 [ 68} Ga]Ga-PSMA-11 生产的小型按需剂量装置，将微流控芯片组装在聚二甲基硅氧烷 (PDMS) 中，将示踪剂生产的所有组件组合在一个集成、紧凑且易于使用的平台中。芯片上放射性核素浓度，以及放射性核素和前体起始材料的混合和反应被纳入。放射性核素来自标准的市售⁶⁸ Ge/ ⁶⁸ Ga 发生器。确定了最佳反应条件，包括前体浓度 (5 μg/mL)、温度 (95 °C) 和反应时间 (1 min)。

结果

片上 SCX 和 SAX 组合柱的总捕集效率大于 70%，可在约 12 分钟内完成。在优化的条件下，[ ⁶⁸ Ga]Ga-PSMA-11 可以在 ~ 12 分钟内从完全发生器洗脱 (1100 MBq [29.7 mCi]) 开始可靠地合成，平均放射化学收率为 70 %，放射化学纯度 > 99 % , 和比活 > 740 MBq/μg (20 mCi/μg)。质量控制测试表明，使用该平台生产的示踪剂满足或超过了 FDA 对人类使用的所有典型要求。

结论

一种简单、低成本、按需剂量的放射合成策略，例如此处介绍的芯片，代表了减少与 PET 成像相关的财务障碍的机会。虽然这项研究的重点是用于 [ ⁶⁸ Ga]Ga-PSMA-11 的设备，但该技术也适用于非常需要低成本、自动化、按需剂量生产的各种其他示踪剂。