A computerized infusion pump for control of tissue tracer concentration during positron emission tomography in vivo pharmacokinetic/pharmacodynamic measurements.

Olof Eriksson,Andreas Wallberg,Bengt Långström,Stina Syvänen,Mats Bergström,Raymond Josephsson

doi:10.1186/1756-6649-8-2

Olof Eriksson, Andreas Wallberg + Show 4 more

Open Access

https://doi.org/10.1186/1756-6649-8-2

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Abstract

BackgroundA computer controlled infusion pump (UIPump) for regulation of target tissue concentration of radioactive compounds was developed for use in biological research and tracer development for PET.MethodsBased on observed tissue or plasma kinetics after a bolus injection of the tracer an algorithm calculates the infusion needed to obtain a specified target kinetic curve. A computer feeds this infusion scheme into an infusion pump connected to an animal via a venous catheter. The concept was validated using [11C]Flumazenil administrated to Sprague-Dawley rats where the whole brain distribution and kinetic of the tracer was measured over time using a microPET-scanner. The accuracy and precision of the system was assessed by producing steady-state levels of the tracer and by mimicking kinetics after oral administration.ResultsVarious kinetic profiles could be generated, including rapid achievement of constant levels, or step-wise increased levels. The resulting tissue curves had low deviation from the target curves according to the specified criteria: AUC (%): 4.2 ± 2.8, Maximal deviation (%): 13.6 ± 5.0 and R2: 0.95 ± 0.02.ConclusionThe UIPump-system is suitable for use in PET-research for assessment of PK/PD properties by simulation of different tracer tissue kinetics in vivo.

Highlights

A computer controlled infusion pump (UIPump) for regulation of target tissue concentration of radioactive compounds was developed for use in biological research and tracer development for Positron Emission Tomography (PET)
Functional imaging for the assessment of the in vivo pharmacokinetics and pharmacodynamics (PK/PD) of drugs either preclinically or in early clinical trials has become an important step in pharmacological research and drug development
With the administration of radiolabeled drugs, PET allows the direct measurement of tissue concentration of radioactivity, and through knowledge of the specific radioactivity, ratio of radioactivity concentration and concentration of non-radioactive compound, the drug concentration kinetic profile can be obtained with high accuracy

Summary

Introduction

A computer controlled infusion pump (UIPump) for regulation of target tissue concentration of radioactive compounds was developed for use in biological research and tracer development for PET. Positron Emission Tomography (PET) is a noninvasive imaging tool that allows the assessment of PK/PD parameters directly at the level of the drug target,. With the administration of radiolabeled drugs, PET allows the direct measurement of tissue concentration of radioactivity, and through knowledge of the specific radioactivity, ratio of radioactivity concentration and concentration of non-radioactive compound, the drug concentration kinetic profile can be obtained with high accuracy. With the administration of a PET tracer with high affinity and specificity for the target, parameters can be extracted from the tissue kinetic profiles which are relevant for target expression, notably binding potential which is proportional to Bmax/kD. It should be possible to generate an i.v. administration scheme which simulates the PK profile obtained from oral administration and thereby direct observe the proper tissue concentration profile in the PET study

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