Interventional therapy of head and neck cancer with lipid nanoparticle-carried rhenium 186 radionuclide

PURPOSE: Minimally invasive interventional cancer therapy with drug-carrying lipid nanoparticles (ie, liposomes) via convection-enhanced delivery by an infusion pump can increase intratumoral drug concentration and retention while facilitating broad distribution throughout solid tumors. The authors investigated the utility of liposome-carrying β-emitting radionuclides to treat head and neck cancer by direct intratumoral infusion in nude rats. MATERIALS AND METHODS: Four groups of nude rats were subcutaneously inoculated with human tongue cancer cells. After tumors reached an average size of 1.6 cm³, the treatment group received an intratumoral infusion of liposomal rhenium-186 (¹⁸⁶Re) (185 MBq [5 mCi]/cm³ tumor). Three control groups were intratumorally infused with unlabeled liposomes, unencapsulated ¹⁸⁶Re-perrhenate, or unencapsulated intermediate ¹⁸⁶Re compound (¹⁸⁶Re-N,N-bis[2-mercaptoethyl]-N′, N′-diethyl-ethylenediamine [BMEDA]). In vivo distribution of ¹⁸⁶Re activity was measured by planar γ-camera imaging. Tumor therapy and toxicity were assessed by tumor size, body weight, and hematology. RESULTS: Average tumor volume in the ¹⁸⁶Re-liposome group on posttreatment day 14 decreased to 87.7% ± 20.1%, whereas tumor volumes increased to 395.0%514.4% on average in the other three groups (P<.001 vs ¹⁸⁶Re-liposome). The ¹⁸⁶Re-liposomes provided much higher intratumoral retention of ¹⁸⁶Re activity, resulting in an average tumor radiation absorbed dose of 526.3 Gy ± 93.3, whereas ¹⁸⁶Re-perrhenate and ¹⁸⁶Re-BMEDA groups had only 3.3 Gy ± 1.2 and 13.4 Gy ± 9.2 tumor doses, respectively. No systemic toxicity was observed. CONCLUSIONS: Liposomal ¹⁸⁶Re effectively treated head and neck cancer with minimal side effects after convection-enhanced interventional delivery. These results suggest the potential of liposomal ¹⁸⁶Re for clinical application in interventional therapy of cancer.