Intraoperative therapy with liposomal drug delivery: Retention and distribution in human head and neck squamous cell carcinoma xenograft model

The focus of this study is to investigate the retention and biodistribution of technetium-99m (^99mTc) labeled liposomes in a human head and neck squamous cell carcinoma (HNSCC) positive surgical margin animal xenograft model. Positive surgical margin (with margin < 1 mm) in HNSCC is associated with significant higher mortality and recurrence rate when compared to clear margin. An immediate intraoperative application of liposome-carried therapeutic agents may treat the residual disease intraoperatively and improve long term survival in these patients. To understand the feasibility of this intraoperative therapy in HNSCC, the in vivo behavior of liposomes after intraoperative administration of ^99mTc-labeled liposomes using non-invasive nuclear imaging was investigated in an animal xenograft model. Neutral and cationic ^99mTc-labeled liposomes of 100 nm, 1 μm and 2 μm in diameter (6 study groups with 4 rats per study group) were injected into a nude rat HNSCC positive surgical margin xenograft model. Intratumoral, locoregional, and systemic retention and distribution of the ^99mTc-liposomes were determined using non-invasive nuclear imaging and post-mortem organ distribution. The ^99mTc-liposomes demonstrated high locoregional retention rate of 55.9 ± 3.7% to 72.9 ± 2.4% at 44 h after intraoperative injection to allow significant radiation to the surgical cavity if therapeutic radionuclides were used. Overall, the cationic liposomes demonstrated higher intratumoral retention rate, and the neutral liposomes showed greater retention in the paratumoral cavity (p < 0.05 respectively). In conclusion, intraoperative therapy with liposome carried radionuclide drug delivery system carries great potential in treating unresectable HNSCC, and further study using therapeutic radionuclide should be explored.