Abstract
PurposeA 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.ResultsDocetaxel 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 MethodsWe 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).ConclusionsWe developed an iodine-docetaxel emulsion and demonstrated that it can be applied to simultaneously achieve CT SLN imaging and local chemotherapy against nodal metastasis.
Highlights
Regional lymph nodes (LNs) are one of the most frequent sites of early carcinoma metastasis
Popliteal LN enhancement on computed tomography (CT) was observed in all healthy rabbits (n=3) and VX2 tumor-implanted rabbits (n=6) 12 hours after injection
The rate of sentinel lymph node (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)
Summary
Regional lymph nodes (LNs) are one of the most frequent sites of early carcinoma metastasis. As nonsurgical or minimally invasive treatments are increasingly performed, the diagnosis and treatment of regional LN metastasis becomes extremely challenging because these procedures often omit LN dissection. Strategies to effectively diagnose and eradicate nodal metastatic tumor cells are extremely important, especially if a non-surgical and/or minimally invasive treatment option is considered. The sentinel lymph node (SLN) is defined as the first LN that directly receives lymph flow from the primary tumor, and is the most likely site of early nodal metastasis. SLN biopsy has been established as an effective method to determine whether surgical LN dissection is necessary, especially in breast cancer and malignant melanoma, and to a lesser extent in other kinds of tumors [6,7,8]
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