摘要
Most techniques for measuring tissue concentrations of drugs are invasive,time-consuming,and often require the removal of tissue or bodyfluids.Optical pharmacokinetics(OP)is a minimally invasive alternative giving an immediate result.Pulses of white light are directed at the tissue of interest using afiber optic probe.Scattered light is detected by a secondfiber immediately adjacent to thefirst in the same probe(separation 1.7 mm).Using the photosensitizer disulfonated aluminium phthalocyanine(AlS_(2)Pc),OP measurements were made in phantoms and on the mouth,stomach,colon,skin,and liver of normal rats 1 and 24 h after intravenous AlS_(2)Pc administration.AlS_(2)Pc concentration was determined by calculating the area under the curve(AUC)in the spectral region around the peak drug absorption or measuring the height of the peak.Spectral baseline interpolation removed the need for pre-drug,control optical measurements.OP measurements correlated well with values from alkali chemical extraction(CE)of the corresponding tissues,(R^(2)0.87=0.97).OP measurements in the mouth also correlated with CE of less accessible internal organs(R^(2)0.77-0.88).In phantoms,the lowest detectable concentration was 0.1μg/g.In vivo,results were limited by the lower accuracy in the CE measurements but were almost certainly comparable.An incidentalfinding was a 12-15nm red shifted component in the spectra observed 1 h after drug administration,suggesting partitioning of the drug in different microenvironment compartments,which could prove to be of considerable interest in future studies.In conclusion,OP shows promise for real-time measurement of concentrations of drugs with suitable absorption peaks.
基金
We thank Dr Stephen Chad Kanick and Dr Robert Parker of the University of Pittsburgh for discussions regarding analytical approaches.The US Department of Health and Human Services National Institutes of Health(NIH)are gratefully acknowledged for their funding of this project(project No.5 U54 CA 104677-05),which was part of the NTROI programme(Network for Translational Research on Optical Imaging).This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.This work was supported by the Experimental Cancer Medicine Centre,University College London.
