Simultaneous sentinel lymph node computed tomography and locoregional chemotherapy for lymph node metastasis in rabbit using an iodine-docetaxel emulsion

Abstract

PURPOSE: A sentinel lymph node (SLN) tracer can gain multi-functionality by combining it with additional components. We developed a SLN tracer consisting of iodine and docetaxel and applied it as a theragnostic nanoparticle to simultaneously perform SLN computed tomography (CT) lymphography and locoregional chemotherapy of the draining lymphatic system.

RESULTS: Docetaxel could be loaded in iodine emulsions at a drug-to-surfactant weight ratio as high as that in the drug formulation Taxotere®. The particle size and drug concentration were stable during storage for up to 3 months in optimized nanoemulsions. Popliteal LN enhancement on CT was observed in all healthy rabbits (n=3) and VX2 tumor-implanted rabbits (n=6) 12 hours after injection. The rate of SLN metastasis was significantly lower in the treatment group (29.4%, 5/17) than in the non-treatment group (70.6%, 12/17) (P=0.038).

MATERIAL AND METHODS: We prepared a nanoemulsion carrying both iodine and docetaxel in a single structure by optimizing the composition of surfactants surrounding the inner iodized oil core. CT was performed 12 hours after subcutaneous injection of the emulsion in healthy rabbits (n=3) and VX2 tumor-implanted rabbits (n=6) for SLN imaging. Next, we tested the effect of treatment by histopathologically assessing the popliteal LN metastasis rate in VX2 tumor-implanted rabbits 7 days after subcutaneous injection of the emulsion (treatment group, n=17) and comparing it with that of non-treatment group rabbits (n=17).

CONCLUSIONS: We developed an iodine-docetaxel emulsion and demonstrated that it can be applied to simultaneously achieve CT SLN imaging and local chemotherapy against nodal metastasis.