Quantitative CT Imaging of the Spatial and Temporal Distribution of Liposomes in a Rabbit Tumor Model

Successful employment of noninvasive imaging techniques to quantitatively assess the in vivo pharmacokinetics and biodistribution of nanoparticle drug delivery systems will facilitate the rational design of novel targeted drug carriers. This study reports on the bulk organ/tissue (liver, kidneys, spleen, tumor and blood) and intratumoral distribution of liposomes containing iohexol and gadoteridol over a 14-day period in VX2 sarcoma-bearing New Zealand White rabbits using computed tomography (CT). The vascular half-life of the liposomes was found to be 63.6 +/- 5.8 h and the maximum tumor-to-muscle iodine concentration ratio of 11.9 +/- 6.0 was measured 7 days postinjection with 1.13 +/- 0.29% ID of liposomes accumulating at the tumor site. The liposomes achieved their highest intratumoral distribution volume ratio at 48 h postadministration, occupying 72 +/- 5% of the total tumor volume. This investigation demonstrated the feasibility of using CT to perform quantitative, volumetric and longitudinal assessment of the pharmacokinetics and biodistribution of iodinated liposomes with sensitivities in the range of mu g/cm(3) while maintaining the ability to identify boundaries of anatomical structures at submillimeter resolution and with imaging time of less than one minute per scan. If successfully approved for clinical adoption, the use of CT imaging to monitor nanoparticulate drug delivery will provide an opportunity for online adjustment of therapeutic regimens and implementation of personalized medicine.