ANSTO's research capabilities, led by the OPAL nuclear research reactor and associated instruments provide access to users investigating areas as diverse as materials, life sciences, climate change and mining/engineering.
Assessing the properties of novel PET tracers using in vivo imaging
Cross disciplinary approaches are a necessity to characterise and validate a novel radiotracer for use in pre-clinical imaging. This involves the characterisation of metabolism and pharmacokinetics of the tracer in plasma as an initial step, utilising the radiochemistry and analytical chemistry aspects of the platform.
Tracer metabolism and pharmacokinetics
Serial time points of whole blood/plasma are collected from cannulated anaesthetised animals. Metabolism is assessed using radio-TLC and radio HPLC on extracted samples to determine a mathematical function modeling metabolism in healthy animals.
In vivo pharmacokinetics of radiotracers using PET
Dynamic acquisitions of PET data are used to determine the in vivo pharmacokinetics of radiotracer within user defined regions of interest. The resulting tissue activity curves for two TSPO radiotracers are shown below (blocking studies with prior administration of cold competing drug show tracer selectivity). As shown below, the study design allows the assessment of selectivity of the novel radiotracers, by comparing the uptake of tracer over time in a normal animal with the change in uptake seen if the animal is given a ‘blocking’ or ‘presaturating’ drug (as reflected in the tissue activity curve data below)
Kinetic modeling: Comparison of binding potentials of novel radiotracers in vivo
One desirable application of the imaging platform is to be able to measure receptor density/affinity changes in a longitudinal study in vivo. Examples for this include using imaging to measure changes in physiology in the same animals over the time that pharmacotherapeutic interventions are given. This requires the development of imaging study designs and analysis techniques tailored to longitudinal imaging
Work conducted within the imaging platform has validated the use of differing kinetic modeling approaches, namely the simplified reference tissue modeling approach and 2 compartment kinetic modeling approach to determine the binding potential kinetic parameter. This allows the use of study designs that don’t require repeated blood sampling to determine binding potentials. The study shown below has allowed us to validate the use of the simplified reference tissue model to quantify binding potential values without blood sampling. This in particular will be used in future for assessing development of neuro-inflammation over time in animal models of neurological/psychiatric disease.