Recent Progress toward Microfluidic Quality Control Testing of Radiopharmaceuticals

Abstract

Radiopharmaceuticals labeled with short-lived positron-emitting or gamma-emitting isotopes are injected into patients just prior to performing positron emission tomography (PET) or single photon emission tomography (SPECT) scans, respectively. These imaging modalities are widely used in clinical care, as well as in the development and evaluation of new therapies in clinical research. Prior to injection, these radiopharmaceuticals (tracers) must undergo quality control (QC) testing to ensure product purity, identity, and safety for human use. Quality tests can be broadly categorized as (i) pharmaceutical tests, needed to ensure molecular identity, physiological compatibility and that no microbiological, pyrogenic, chemical, or particulate contamination is present in the final preparation; and (ii) radioactive tests, needed to ensure proper dosing and that there are no radiochemical and radionuclidic impurities that could interfere with the biodistribution or imaging. Performing the required QC tests is cumbersome and time-consuming, and requires an array of expensive analytical chemistry equipment and significant dedicated lab space. Calibrations, day of use tests, and documentation create an additional burden. Furthermore, in contrast to ordinary pharmaceuticals, each batch of short-lived radiopharmaceuticals must be manufactured and tested within a short period of time to avoid significant losses due to radioactive decay. To meet these challenges, several efforts are underway to develop integrated QC testing instruments that automatically perform and document all of the required tests. More recently, microfluidic quality control systems have been gaining increasing attention due to vastly reduced sample and reagent consumption, shorter analysis times, higher detection sensitivity, increased multiplexing, and reduced instrumentation size. In this review, we describe each of the required QC tests and conventional testing methods, followed by a discussion of efforts to directly miniaturize the test or examples in the literature that could be implemented for miniaturized QC testing.

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“…The radiochemical purity of a radiotracer is the fraction of the total radioactivity in the desired chemical form. The radiochemical impurities have a variety reason including disintegration due to the action of the solvent, change in temperature or pH, exposure to light, the presence of oxidizing or reducing agents in the formulation of a kit, incomplete reaction and radiolysis 20 . The presence of radiochemical impurities during the radiolabeling reaction can reduced the quality of imaging due to a decrease in the target to nontarget ratio.…”

18F-labelling innovations and their potential for clinical application

“…In spite of all those difficulties, several syntheses of clinically relevant 18 Last not least, another serious demand with regard to the production by microfluidics is the fulfilment of pharmaceutical regulations [241]. This includes the qualification of starting materials, the in-process control and particularly the quality control of single batch (dose-on-demand) productions [210,242,243].…”

Plastic Scintillator‐Based Microfluidic Devices for Miniaturized Detection of Positron Emission Tomography Radiopharmaceuticals

“…Several examples of microfluidic or miniaturised radiodetectors have been demonstrated, with varying sensitivities, fabrication processes, and detection times that are summarised in a recent review by Ha et al . However, none of these are optimal for this application.…”