Abstract
Intravenous chemotherapy has poor access to metastatic lymph nodes (LNs) and is limited by short-lived drug concentrations. Here, we describe the administration of chemotherapy via the lymphatic network as a new concept for the prevention and treatment of metastatic LNs. A metastatic LN can be treated by the injection of drugs into an upstream LN, either the sentinel LN (SLN) or another upstream LN. In a mouse model, tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis to the proper axillary LN (PALN). Two routes were used for drug delivery to the PALN, namely from the SiLN and from the accessory axillary LN (AALN). We found that tumor masses were formed in lymphatic vessels between the SiLN and PALN. The flow of fluorescent solution injected into the SiLN towards the PALN decreased with tumor mass formation. Delivery from the AALN (free of metastatic tumor cells) to the PALN was identified as an alternative route. Intranodal injection can deliver high concentrations of drugs to secondary metastatic LNs. The study advocates a new concept for the prevention and treatment of metastatic lymph nodes whereby drugs injected into upstream lymph nodes can reach metastatic lymph nodes via the lymphatic network.
Highlights
Intravenous chemotherapy has poor access to metastatic lymph nodes (LNs) and is limited by shortlived drug concentrations
Intravenous chemotherapy cannot reach the metastases because small molecules, such as anti-cancer drugs, in the interstitium are preferentially re-absorbed into blood capillaries; it is difficult to maintain a high concentration of drug at the target site[3]
The subiliac LN (SiLN) was inoculated with tumor cells and defined as the sentinel LN (SLN); the proper axillary LN (PALN) was defined as the downstream secondary LN; and the axillary LN (AALN) was defined as an upstream LN that was free from metastases
Summary
Intravenous chemotherapy has poor access to metastatic lymph nodes (LNs) and is limited by shortlived drug concentrations. We describe the administration of chemotherapy via the lymphatic network as a new concept for the prevention and treatment of metastatic LNs. A metastatic LN can be treated by the injection of drugs into an upstream LN, either the sentinel LN (SLN) or another upstream LN. Tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis to the proper axillary LN (PALN). Intranodal injection can deliver high concentrations of drugs to secondary metastatic LNs. The study advocates a new concept for the prevention and treatment of metastatic lymph nodes whereby drugs injected into upstream lymph nodes can reach metastatic lymph nodes via the lymphatic network.
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