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

Abstract

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 beta-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 cm(3), the treatment group received an intratumoral infusion of liposomal rhenium-186 ((186)Re) (185 MBq [5 mCi]/cm(3) tumor). Three control groups were intratumorally infused with unlabeled liposomes, unencapsulated (186)Re-perrhenate, or unencapsulated intermediate (186)Re compound ((186)Re-N,N-bis[2-mercaptoethyl]-N',N'-diethyl-ethylenediamine [BMEDA]). In vivo distribution of (186)Re activity was measured by planar gamma-camera imaging. Tumor therapy and toxicity were assessed by tumor size, body weight, and hematology.

Results: Average tumor volume in the (186)Re-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 (186)Re-liposome). The (186)Re-liposomes provided much higher intratumoral retention of (186)Re activity, resulting in an average tumor radiation absorbed dose of 526.3 Gy +/- 93.3, whereas (186)Re-perrhenate and (186)Re-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 (186)Re effectively treated head and neck cancer with minimal side effects after convection-enhanced interventional delivery. These results suggest the potential of liposomal (186)Re for clinical application in interventional therapy of cancer.

Figure 1

Average tumor growth trend of all four groups (A) and tumor growth trend of each individual tumor in each animal in ¹⁸⁶Re-liposome group (B).

Figure 1

Average tumor growth trend of all four groups (A) and tumor growth trend of each individual tumor in each animal in ¹⁸⁶Re-liposome group (B).

Figure 2

Comparison of the average percent of injected radioactivity present in tumors (A) and overall total body activity (B) in each group over time. The % injected activity after each injection was compared with the total activity that had already been injected into each tumor, but does not include the radioactivity which has not been injected into each animal yet.

Figure 2

Comparison of the average percent of injected radioactivity present in tumors (A) and overall total body activity (B) in each group over time. The % injected activity after each injection was compared with the total activity that had already been injected into each tumor, but does not include the radioactivity which has not been injected into each animal yet.

Figure 3

Planar gamma camera images depicting the distribution of ¹⁸⁶Re-activity at various time points after treatment infusion for each study group. There was much higher retention and slower clearance of ¹⁸⁶Re-liposomes in the tumor region compared with ¹⁸⁶Re-BMEDA and ¹⁸⁶Re-perrhenate. (White Arrow-Tumor, Short Arrow-Standard, Grey Arrow-Stomach, Arrowhead-Kidney)

Figure 4

H&E stained sections from control animal (B, D, F) and from ¹⁸⁶Re-liposome treated animal (A, C, E) at 1×, 4×, and 20× magnifications.