Laboratory investigation
Interventional Therapy of Head and Neck Cancer with Lipid Nanoparticle–carried Rhenium 186 Radionuclide

https://doi.org/10.1016/j.jvir.2010.02.027Get rights and content

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.

Section snippets

Head and Neck SCC Xenografts in Nude Rats

Animal experiments were performed according to the National Institutes of Health Animal Care and Use Guidelines and were approved by our institutional animal care committee. During each animal handling procedure, animals were anesthetized by inhalation of 1%–3% isoflurane (Vedco, Saint Joseph, Missouri) in 100% oxygen with use of a veterinary inhalant anesthesia machine (Bickford, Wales Center, New York).

The head and neck SCC xenograft model used here has been previously reported (18). In

Tumor Volumes in 186Re-liposome Treatment Group and Control Groups

On the day of treatment infusion (ie, day 0; average body weight, 238.1 g ± 35.9), the average tumor volumes for groups 1, 2, 3, and 4 were 1.50 cm3 ± 0.52, 1.69 cm3 ± 0.43, 1.79 cm3 ± 0.39, and 1.72 cm3 ± 0.45, respectively. Figure 1a shows the average tumor volumes for each treatment group over the duration of the study. The average tumor volume of the 186Re-liposome treatment group decreased to 87.7% ± 20.1% of the pretreatment volume by day 14 (P < .001 vs control groups). The rate of tumor

Discussion

Local 186Re retention in the tumor was much higher when delivered by a liposome nanocarrier, resulting in a 150-fold greater tumor-absorbed radiation dose in the 186Re-liposome group than in other 186Re groups. This high dose resulted in drastically reduced tumor size and rate of tumor growth in 186Re-liposome–treated animals. A better intratumoral dispersion with 186Re-liposomes may have also contributed to the effective tumor therapy (10). Observations of the 186Re-liposome–treated tumors

References (33)

  • K. Hong et al.

    Technology insight: image-guided therapies for hepatocellular carcinoma—intra-arterial and ablative techniques

    Nature Clin Pract

    (2006)
  • J. Zweit

    Radionuclides and carrier molecules for therapy

    Phys Med Biol

    (1996)
  • W.V. Prestwich et al.

    Beta dose point kernels for radionuclides of potential use in radioimmunotherapy

    J Nucl Med

    (1989)
  • D. Firusian et al.

    An early phase II study of intratumoral P-32 chromic phosphate injection therapy for patients with refractory solid tumors and solitary metastases

    Cancer

    (1999)
  • V.P. Torchilin

    Recent advances with liposomes as pharmaceutical carriers

    Nature Rev Drug Discov

    (2005)
  • O.C. Farokhzad et al.

    Impact of nanotechnology on drug delivery

    ACS Nano

    (2009)
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    This study was supported by National Cancer Institute/National Institutes of Health Grant R01 CA131039 to A.B. None of the authors have identified a conflict of interest.

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