Microfluidic beta and conversion electron radiation detector for preclinical pharmacokinetic studies with PET and SPECT radiotracers

Convert, Laurence; Girard-Baril, F.; Boisselle, V.; Pratte, J.‐F.; Fontaine, R.; Aimez, Vincent; Charette, Paul G.

doi:10.1109/nssmic.2010.5874155

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…28,29 In previous work, we described the use of KMPR as a structural material for microfluidic devices 30 and prototype chips were investigated for charged particles detection. 31,32 We also proposed a method to render KMPR hemocompatible. 33 In this work, the fabrication process of an optimized device is detailed, including the microfluidics and contact to the underlying detection electronics.…”

Section: Prior Artmentioning

confidence: 99%

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Blood compatible microfluidic system for pharmacokinetic studies in small animals

et al. 2012

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New radiotracer developments for nuclear medicine imaging require the analysis of blood as a function of time in small animal models. A microfluidic device was developed to monitor the radioactivity concentration in the blood of rats and mice in real time. The microfluidic technology enables a large capture solid angle and a reduction in the separation distance between the sample and detector, thus increasing the detection efficiency. This in turn allows a reduction of the required detection volume without compromising sensitivity, an important advantage with rodent models having a small total blood volume (a few ml). A robust fabrication process was developed to manufacture the microchannels on top of unpackaged p-i-n photodiodes without altering detector performance. The microchannels were fabricated with KMPR, an epoxy-based photoresist similar to SU-8 but with improved resistance to stress-induced fissuring. Surface passivation of the KMPR enables non-diluted whole blood to flow through the channel for up to 20 min at low speed without clotting. The microfluidic device was embedded in a portable blood counter with dedicated electronics, pumping unit and computer control software for utilisation next to a small animal nuclear imaging scanner. Experimental measurements confirmed model predictions and showed a 4- to 19-fold improvement in detection efficiency over existing catheter-based devices, enabling a commensurate reduction in sampled blood volume. A linear dose-response relationship was demonstrated for radioactivity concentrations typical of experiments with rodents. The system was successfully used to measure the blood input function of rats in real time after radiotracer injection.

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Section: Prior Artmentioning

confidence: 99%

“…The microchannel walls were made larger than the grid lines (500 mm wide) to ensure good sealing. Unlike in our previous designs, 31,32 metallic tracks were added to displace the anode contact away from the microchannel, simplifying wire bonding and optimizing the detection area (Fig. S1B in the ESI{).…”

Section: Microfluidic Chip Fabrication Processmentioning

confidence: 99%

Blood compatible microfluidic system for pharmacokinetic studies in small animals

et al. 2012

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“…In previous work, our group built a microfluidic channel directly above an unpackaged p-i-n silicon photodiode array, eliminating all unnecessary interfaces between blood and the photodiode detection layer to overcome these limitations (24,25). We also proposed a method to improve the blood compatibility of the microchannel polymer building material (26).…”

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confidence: 99%

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies

et al. 2016

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Small-animal nuclear imaging modalities have become essential tools in the development process of new drugs, diagnostic procedures, and therapies. Quantification of metabolic or physiologic parameters is based on pharmacokinetic modeling of radiotracer biodistribution, which requires the blood input function in addition to tissue images. Such measurements are challenging in small animals because of their small blood volume. In this work, we propose a microfluidic counting system to monitor rodent blood radioactivity in real time, with high efficiency and small detection volume (∼1 μL). Methods: A microfluidic channel is built directly above unpackaged p-i-n photodiodes to detect β-particles with maximum efficiency. The device is embedded in a compact system comprising dedicated electronics, shielding, and pumping unit controlled by custom firmware to enable measurements next to small-animal scanners. Data corrections required to use the input function in pharmacokinetic models were established using calibrated solutions of the most common PET and SPECT radiotracers. Sensitivity, dead time, propagation delay, dispersion, background sensitivity, and the effect of sample temperature were characterized. The system was tested for pharmacokinetic studies in mice by quantifying myocardial perfusion and oxygen consumption with 11 C-acetate (PET) and by measuring the arterial input function using 99m TcO 4 − (SPECT). Results: Sensitivity for PET isotopes reached 20%-47%, a 2-to 10-fold improvement relative to conventional catheter-based geometries. Furthermore, the system detected 99m Tc-based SPECT tracers with an efficiency of 4%, an outcome not possible through a catheter. Correction for dead time was found to be unnecessary for small-animal experiments, whereas propagation delay and dispersion within the microfluidic channel were accurately corrected. Background activity and sample temperature were shown to have no influence on measurements. Finally, the system was successfully used in animal studies. Conclusion: A fully operational microfluidic blood-counting system for preclinical pharmacokinetic studies was developed. Microfluidics enabled reliable and high-efficiency measurement of the blood concentration of most common PET and SPECT radiotracers with high temporal resolution in small blood volume. Radi onuclide-based molecular imaging using PET and SPECT is a leading diagnostic tool in oncology, cardiology, and neurology (1). In research applications, small-animal models are needed to facilitate the development of new drugs, radiotracers, and therapies that can eventually be translated to humans (2). Quantification of metabolic or physiologic disorders using radiotracer pharmacokinetic models requires dynamic blood analysis in addition to tissue imaging data (3). Whole-blood radioactivity as a function of time, the so-called arterial input function (AIF), can be extracted from PET images (4,5), using an intravascular b-microprobe (6,7) or an external blood counter connected to an artery via a catheter (8-10). Fo...

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Monitoring of Microfluidics Systems for PET Radiopharmaceutical Synthesis Using Integrated Silicon Photomultipliers

et al. 2019

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Microfluidic beta and conversion electron radiation detector for preclinical pharmacokinetic studies with PET and SPECT radiotracers

Cited by 3 publications

References 8 publications

Blood compatible microfluidic system for pharmacokinetic studies in small animals

Blood compatible microfluidic system for pharmacokinetic studies in small animals

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies

Monitoring of Microfluidics Systems for PET Radiopharmaceutical Synthesis Using Integrated Silicon Photomultipliers

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