Abstract
Over the past several years there has been an explosion of interest in exploiting Cerenkov radiation to enable in vivo and intraoperative optical imaging of subjects injected with trace amounts of radiopharmaceuticals. At the same time, Cerenkov luminescence imaging (CLI) also has been serving as a critical tool in radiochemistry, especially for the development of novel microfluidic devices for producing radiopharmaceuticals. By enabling microfluidic processes to be monitored non-destructively in situ, CLI has made it possible to literally watch the activity distribution as the synthesis occurs, and to quantitatively measure activity propagation and losses at each step of synthesis, paving the way for significant strides forward in performance and robustness of those devices. In some cases, CLI has enabled detection and resolution of unexpected problems not observable via standard optical methods. CLI is also being used in analytical radiochemistry to increase the reliability of radio-thin layer chromatography (radio-TLC) assays. Rapid and high-resolution Cerenkov imaging of radio-TLC plates enables detection of issues in the spotting or separation process, improves chromatographic resolution (and/or allows reduced separation distance and time), and enables increased throughput by allowing multiple samples to be spotted side-by-side on a single TLC plate for parallel separation and readout. In combination with new multi-reaction microfluidic chips, this is creating a new possibility for high-throughput optimization in radiochemistry. In this mini review, we provide an overview of the role that CLI has played to date in the radiochemistry side of radiopharmaceuticals.
Highlights
The use of Cerenkov luminescence imaging (CLI) in the field of molecular imaging began with the realization that charged particles emitted by F-18 and other positron emitting sources have enough energy to produce Cerenkov light as they travel through matter [1,2,3,4]
If this light can be detected, images of the spatial and temporal distribution of radiolabeled probes can be obtained nondestructively [1]. This realization led to a flurry of new applications including in vivo CLI in small animals or patients, new methods for visualization of radioactivity distribution in microscale devices used for radiopharmaceutical production, and alternative methods for readout of radio-thin layer chromatography plates
Some of the earliest microfluidic devices capable of performing multi-step syntheses of radiopharmaceuticals were fabricated from polydimethylsiloxane (PDMS), a transparent elastomer widely used in microfluidics due to the relatively simple fabrication process and ability to integrate microvalves for fluid manipulation
Summary
The use of Cerenkov luminescence imaging (CLI) in the field of molecular imaging began with the realization that charged particles emitted by F-18 and other positron emitting sources have enough energy to produce Cerenkov light as they travel through matter [1,2,3,4]. If this light can be detected, images of the spatial and temporal distribution of radiolabeled probes can be obtained nondestructively [1] This realization led to a flurry of new applications including in vivo CLI in small animals or patients (reviewed in [5,6,7,8,9,10,11,12,13,14,15]), new methods for visualization of radioactivity distribution in microscale devices used for radiopharmaceutical production, and alternative methods for readout of radio-thin layer chromatography (radio-TLC) plates. We discuss several of these technologies where CLI has played an important role in their development
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