title: Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies.
abstract: 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)TcO4 (-) (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sherbrooke Molecular Imaging Centre of CRCHUS and Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada Laboratoire Nanotechnologies Nanosystèmes (LN2)-CNRS UMI-3463, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and Institut Interdisciplinaire d'Innovation Technologique (3IT), Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Convert
authors.affiliation: Sherbrooke Molecular Imaging Centre of CRCHUS and Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Réjean
authors.initials: R
authors.lastname: Lebel
authors.affiliation: Sherbrooke Molecular Imaging Centre of CRCHUS and Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gascon
authors.affiliation: Institut Interdisciplinaire d'Innovation Technologique (3IT), Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Réjean
authors.initials: R
authors.lastname: Fontaine
authors.affiliation: Institut Interdisciplinaire d'Innovation Technologique (3IT), Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Pratte
authors.affiliation: Laboratoire Nanotechnologies Nanosystèmes (LN2)-CNRS UMI-3463, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and Institut Interdisciplinaire d'Innovation Technologique (3IT), Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Charette
authors.affiliation: Laboratoire Nanotechnologies Nanosystèmes (LN2)-CNRS UMI-3463, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and Institut Interdisciplinaire d'Innovation Technologique (3IT), Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Aimez
authors.affiliation: Sherbrooke Molecular Imaging Centre of CRCHUS and Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada Roger.Lecomte@USherbrooke.ca.
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000295:instrumentation*; D003199:Computer Systems; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation; D004867:Equipment Design; D019544:Equipment Failure Analysis; D056656:Lab-On-A-Chip Devices; D051379:Mice; D008807:Mice, Inbred BALB C; D008832:Microchemistry / Q000295:instrumentation; D010599:Pharmacokinetics; D049268:Positron-Emission Tomography / Q000295:instrumentation*; D011874:Radiometry / Q000295:instrumentation*; D019275:Radiopharmaceuticals / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015899:Tomography, Emission-Computed, Single-Photon / Q000295:instrumentation*
chemical_list: D019275:Radiopharmaceuticals
keywords: arterial input function; microfluidic; pharmacokinetic studies; small animal PET; small animal SPECT