Radiochemistry on chip: towards dose-on-demand synthesis of PET radiopharmaceuticals

Arima, Valentina; Pascali, Giancarlo; Lade, Oliver; Kretschmer, Hans R.; Bernsdorf, Ingo; Hammond, Victoria J.; Watts, Paul; Leonardis, Francesco De; Tarn, Mark D.; Pamme, Nicole; Cvetković, Benjamin Z.; Dittrich, Petra S.; Vasovic, Nikola; Duane, Russell; Jakšić, A.; Zacheo, Antonella; Zizzari, Alessandra; Marra, Lucia; Perrone, Elisabetta; Salvadori, Piero A.; Rinaldi, R.

doi:10.1039/c3lc00055a

Cited by 60 publications

(48 citation statements)

References 17 publications

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“…Available literature has demonstrated that this approach might be feasible for producing a stream of purified FDG out of a continuously running MCS apparatus. This prototype actually reported the integration of the whole production process in a very compact flow system that generated a continuous stream of product, starting from a continuous feed of radiofluorination complex and chemicals (Arima et al 2013) (Fig. 8.21).…”

Section: Microfluidics In Radiochemistry Integrated Systemsmentioning

confidence: 99%

Microfluidics in Planar Microchannels: Synthesis of Chemical Compounds On-Chip

Arima

Watts

Pascali

2014

Lab-on-a-Chip Devices and Micro-Total Analysis Systems

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Microreactors are a wide class of devices that are currently playing a prominent role in several research fields such as biology, medicine, food chemistry, environmental analysis, up to the production of compounds in organic chemistry. Several typologies of microreactors have been produced with tubular or planar shapes, of different materials and designs. In this chapter, an overview of planar microchannel-based microreactors and their application to organic chemistry is given. Initially, after recalling the main theoretical parameters of microfluidics, an introduction of the proposed technology and the main requirements to perform mixing, which is essential to perform chemical synthesis on-chip, is presented. Silicon and glass microreactors, the most common planar systems for organic chemistry, are described with the aim of pointing out the most important parameters to be taken into consideration in the planning of a specific microreactor to be used for mixing, purification or crystallization of chemicals at the microscale. Then, several applications of initially described microreactors to organic chemistry for research applications are given. In the next section, the use of planar microchannel microreactors in the field of radiochemistry is reported. The radiopharmaceutical application is not casual, being a sector in which the microreactor technology is very promising, due to the need of quickly producing small and fresh amounts of products in a controlled environment. Finally, for completeness, other approaches beyond planar microchannels are mentioned: mesoreactors towards industrial level synthesis and micro-vessels for radiochemistry.

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Section: Microfluidics In Radiochemistry Integrated Systemsmentioning

confidence: 99%

Microfluidics in Planar Microchannels: Synthesis of Chemical Compounds On-Chip

Arima

Watts

Pascali

2014

Lab-on-a-Chip Devices and Micro-Total Analysis Systems

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“…The first batch microfluidic synthesis of [ 18 F]FDG was demonstrated in a polydimethylsiloxane (PDMS) chip with 40 nL reaction volume [14]. Microvalves [19], Copyright © 2013 Elsevier, Inc.) (g) EWOD chip with reaction volume ranging from 2 to 17 μL were used to close the reactor during reaction steps, and the permeability of the PDMS enabled escape of vapor for solvent exchange processes.…”

Section: Platforms For Microliter Volume Synthesismentioning

confidence: 99%

Advantages of Radiochemistry in Microliter Volumes

Keng

Sergeev

Dam

2016

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

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Positron emission tomography (PET) provides quantitative 3D visualization of physiological parameters (e.g., metabolic rate, receptor density, gene expression, blood flow) in real time in the living body. By enabling measurement of differences in such characteristics between normal and diseased tissues, PET serves as vital tool for basic research as well as for clinical diagnosis and patient management. Prior to a PET scan, the patient is injected with a short-lived tracer labeled with a positron-emitting isotope. Safe preparation of the tracer is an expensive process, requiring specially trained personnel and high-cost equipment operated within hot cells. The current centralized manufacturing strategy, in which large batches are prepared and divided among many patients, enables the most commonly used tracer (i.e., [ 18 F]FDG) to be obtained at an affordable price. However, as the diversity of tracers increases, other strategies for cost reduction will become necessary. This challenge is being addressed by the development of miniaturized radiochemistry instrumentation based on microfluidics. These compact systems have the potential to significantly reduce equipment cost and shielding while increasing diversity of tracers produced in a given facility. The most common approach uses "flow-through" microreactors, which leverage the ability to precisely control reaction conditions to improve synthesis times and yields. Several groups have also developed "batch" microreactors which offer significant additional advantages such as reduced reagent consumption, simpler purifications, and exceptionally high specific activity, by reducing operating volumes by orders of magnitude. In this chapter, we review these "batch" approaches and the advantages of using small volumes, with special emphasis on digital microfluidics, in which reactions have been performed with volumes as low as~1 μL.

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“…This system should implement the reduction to the minimum possible of the amounts of radioactivity and chemicals needed in the preparation, added to an overall simplification of the production process. Such conceptual process can be defined as "Dose On Demand" (DOD) [3,4,5]: the operation of producing a radiopharmaceutical in the shortest time possible, using the minimum amount of chemicals and radioactivity strictly needed for the production of the single (or few) imaging dose (s) required.…”

Section: Dod Featuresmentioning

confidence: 99%

How Far Are We from Dose On Demand of Short-Lived Radiopharmaceuticals?

Pascali

Matesic

2016

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

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PET radiopharmaceuticals are currently produced using a centralized approach, which makes sustainable the distribution to few imaging centers of an only small set of tracers (virtually only [18 F]FDG). However, a wider set of structures have demonstrated a potential applicability for imaging in a specific manner several disease condition. In order to allow this wider and more personalized use of PET imaging, the production paradigms need to be changed. In this contribution we will explain how Dose-On-Demand systems can be conceptualized and what are the challenges that are still to be overcome in order for such approach to be of widespread utility.

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Radiochemistry on chip: towards dose-on-demand synthesis of PET radiopharmaceuticals

Cited by 60 publications

References 17 publications

Microfluidics in Planar Microchannels: Synthesis of Chemical Compounds On-Chip

Microfluidics in Planar Microchannels: Synthesis of Chemical Compounds On-Chip

Advantages of Radiochemistry in Microliter Volumes

How Far Are We from Dose On Demand of Short-Lived Radiopharmaceuticals?

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