Feasibility of Using a Two-Wavelength Photometer to Estimate the Concentration of Circulating Near-Infrared Extinguishing Nanoparticles

We demonstrate a photometer based on pulse oximeter technology designed to test the feasibility of using non-invasive optics to quantify in vivo circulation parameters of optically-active particles by measuring changes in optical extinction introduced by the particles in a murine animal model. A real-time estimate of relative concentration was produced by collecting log-scaled bandpass pulsatile and non-pulsatile intensity (760 nm or 940 nm) near the extinction peak of the employed gold nanoshells and mathematically subtracting the pre-injection intensity through the murine subject. The circulation half-lives in four mice were estimated between 3 and 43 minutes compared to direct optical measurement of 5 mu L blood draws with UV/Vis spectrophotometry which demonstrated nanoparticle extinctions ranging from 0.246 to 7.408 optical density (OD). A linear model fit relating the two methods produced an R-2 value of 0.75. The 1.795 OD negative bias (-4.98 x 10(9) nanoparticles/ml) between the two methods describes the 35.5% (or 12.0 minutes) average error of prediction of the half-life. This report demonstrates that the circulation parameters of optically-active particles employed at therapeutically-relevant concentrations can be monitored in real-time using non-invasive optical techniques and advises further refinement.