Abstract LBA048: Lymph node metastasis targeted intranodal delivery of docetaxel improves treatment outcome

Abstract

Abstract Despite recent advances in diagnostic modalities and cancer treatment guidelines, systemic chemotherapy for the lymph node (LN) metastasis has poor treatment efficacy using conventional drugs. Therefore, a novel method, lymphatic drug delivery system (LDDS), has been proposed in a pre-clinical experiment that directly injects the anticancer drug into sentinel LNs to deliver into their downstream LNs, aiming to inhibit tumor cell growth in those LNs. The injection duration of chemotherapy drugs using the LDDS will be less than the intratumoral or intralesion methods used in the clinic, and systemic toxicity will be less than tumor-targeted therapy or systemic chemotherapy. Our previous results indicated that the treatment efficacy increased in LDDS treated groups than systemic delivery. Here, we show the improvement of treatment efficacy by increasing osmotic pressure and viscosity of the drug solvent delivered by LDDS using the metastatic LN mouse model. First, a metastatic LN mouse model was created by inoculating luciferase-expressing tumor cells into subiliac LN (SiLN) of MXH10/Mo/lpr mouse to induce metastasis into the proper axillary LN (PALN). Next, 10 mg/kg docetaxel (DTX) with increased osmotic pressure and viscosity were injected into tumor-inoculated SiLN with an injection rate of 2400 μL/min on day 7 post-inoculation to inhibit tumor cell growth in the inoculation and metastatic site. Luciferase activity decreases in PALNs and SiLNs were observed in groups between 1140 kPa, 1960 kPa, and 2780 kPa (4, 11, and 38 mPa·s) groups without inducing any side effects. By histology, no tumor cells were confirmed in those LNs of the 1960 kPa group. Then, DTX at 1960 kPa, 11 mPa·s was injected into tumor-inoculated SiLN on day 21 post-inoculation with different injection speeds and volumes. We found that DTX at 1960 kPa, 11 mPa·s injected at the injection rate of 200 μL/min with 400 μL volume, can inhibit tumor cell growth in the PALN and delay tumor growth SiLN. Furthermore, the antitumor effects depended on the tumor progression stage in the LNs, and the injection rates and volumes of administered drugs. We anticipate these optimal ranges as a starting point for developing more effective drug regimens to treat metastatic LNs with the LDDS. Moreover, administrable drugs in this novel method of ultrasound-guided LDDS or LDDS at intra-operative or image-guided surgery are not limited only to anticancer agents. Citation Format: Ariunbuyan Sukhbaatar, Shouta Sora, Mori Shiro, Tetsuya Kodama. Lymph node metastasis targeted intranodal delivery of docetaxel improves treatment outcome [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA048.