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In vivo sampling for pharmacokinetic studies in small experimental animals: a combination of microdialysis, planar
Merja Haaparanta1, Tove Grönroos, Päivi Marjamäki
1Turku PET Centre, Medicity Research Laboratory/PET, Turku, Finland. mehaaso@utu.fi
Purpose:
We describe a method for measuring the pharmacokinetics of positron emission tomography (PET) tracers during rat studies using microdialysis (MD) in combination with planar chromatography and digital autoradiography with a phosphoimager plate (DAR).
Procedures:
An MD probe was inserted into the jugular vein of the rat and perfused with physiological buffer solution (n>/=3). An (18)F-labeled radiopharmaceutical was injected intravenously, and dialysate fractions were collected, measured for radioactivity, and applied on a chromatography plate. This plate was exposed with an imaging plate for radioactivity imaging.
Results:
Time activity curves for unbound, unchanged tracer and metabolites were determined. The amount of unchanged tracer in the last MD fraction was compared with the amount in the plasma sample collected after sacrifice of the animal.
Conclusion:
MD continuously samples and monitors the amount of unbound tracer in the blood from one single experimental animal. MD combined with planar chromatography and DAR is a highly sensitive and linear method for simultaneous analysis of PET tracers and their metabolites in blood.
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