Abstract #5597: Interventional therapy of head and neck cancer with lipid nanoparticle-carried rhenium-186 radionuclide

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO Purpose: Focal cancer therapy maximizes therapeutic benefits while greatly limiting normal tissue toxicity. Direct, intratumoral infusion of a lipid nanoparticle (liposome) drug carrier system can provide profound elevation of intratumoral drug concentration and retention while facilitating broad distribution throughout solid tumors. Liposomes containing beta-emitting radionuclides have a therapeutic range extending several mm and ultimately deliver high intratumoral radiation doses. Since squamous cell carcinoma of the head and neck is predominantly a locoregional disease, we investigated the therapeutic utility of liposomes carrying beta-emitting radionuclides to treat this cancer when administered by direct, intratumoral infusion. Experimental Design: Four groups of nude rats were subcutaneously inoculated with human tongue cancer cells (SCC-4). After the tumors reached an average size of 1.6 cm3, treatment group received an intratumoral infusion of liposomal rhenium-186 (5 mCi/cm3 tumor) (n=6). Control groups received an intratumoral infusion of either unlabeled liposomes (n=6), 186Re-perrhenate (n=6), or an intermediate 186Re compound (186Re-BMEDA) (n=5) with either the same lipid amount or same 186Re activity. In vivo distribution of 186Re activity was measured by planar gamma camera imaging. Tumor therapy and toxicity were assessed by measurements of tumor size, body weight, and hematology. Animals in control groups were euthanized at day 14 due to excessive tumor burden. The 186Re-liposome treated group was followed for 43 days. Tumors and major organs from all groups were evaluated by histopathology. Results: Tumor volumes on post-treatment day 14 had increased to 514.4±59.1% in the unlabeled liposome group, 426.4±83.0% in the 186Re-perrhenate group, and 395.0±41.2% in the 186Re-BMEDA group. The tumor volume of the 186Re-liposome group dropped to 87.7±20.1% (P<0.001 vscontrol groups). At 43 days, 3 tumors in the 186Re-liposome treated group showed sustained shrinkage (50.8±10.4%), one tumor showed a stable volume (115.3%), and two tumors had delayed growth (225.5±2.5%) at a much slower rate than control groups. 186Re-liposomes provided much better intratumoral retention and dispersion of radioactivity, resulting in an average tumor absorbed radiation dose of 526.3±93.3 Gy, whereas 186Re-perrhenate and 186Re-BMEDA groups had only 3.3±1.2 and 13.4±9.2 Gy tumor doses respectively. All groups showed consistent increases in body weight. No systemic toxicity was observed in any animals. Conclusions: Liposomal 186Re was very effective in suppressing tumor growth after intratumoral infusion, while non-liposomal 186Re showed no therapeutic benefit. Given the excellent tumor suppression and minimal side effects seen in the current study, 186Re-liposomes appear to have great potential for clinical application in treatment of head and neck cancer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5597.