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  • Theranostic Nanoparticle-Mediated Tumor Ablation in a Rat Model of Metastatic Spine Disease

    Final Number:

    Mari L. Groves MD; Patricia L. Zadnik BA; Rachel Sarabia-Estrada DVM PhD; Camilo A. Molina BA; Michele E Wabler BS; Jana Mihalic; Robert Ivkov PhD; Daniel M. Sciubba BS MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: Among the 1.5 million new cases of cancer diagnosed annually, 30-90% of patients experience spinal metastasis. [1,2] The purpose of this study was to use an animal model of metastatic spine disease to investigate nanoparticle-based tumor thermoablation as a treatment modality for metastatic spine disease. Ferromagnetic nanoparticles (NP) can be delivered by injection to target cancer tissue, and when exposed to an alternating magnetic field (AMF), the magnetic materials can generate thermoablative heat. [3,4]

    Methods: Seventy-four female Fisher rats were divided into two groups (Group-1, n=18 and Group-2, n=56). Both groups underwent a transperitoneal approach for implantation of rat breast-adenocarcinoma tissue (CRL-1666) into the L6 vertebral body. All animals received intratumoral NP injections (0.4 mg/cm3) at day nine. Group-1 animals were sacrificed at 1, 3, 6, 12, 24, and 48 hours following NP injection. Lung, liver, and spleen were harvested for histology. Inductively-coupled plasma mass spectrometry (ICP-MS) was performed on blood and CSF samples to determine iron concentration. Group-2 animals were randomized to AMF only, NP/AMF, NP only and no treatment. Rectal temperature was monitored during treatment. Motor and sensory function was assessed after treatment.

    Results: Group-1 distribution analysis at 1,3,6,12,24, and 48 hours demonstrated linear clearance of iron from blood and CSF as measured by ICP-MS. There was an absence of NP in the spinal cord, lung, liver, or spleen as demonstrated by H&E and Prussian blue staining at all time points. All Group-2 animals survived NP and AMF therapy and remained ambulatory at 24 hours post AMF therapy. There was no difference in rectal temperature between NP and non-NP groups receiving AMF therapy.

    Conclusions: NP and AMF therapy to spinal column tumors is a safe treatment modality that results in limited systemic distribution, no immediate neurologic deficit and minimal change to core temperature in a rat intravertebral tumor model.

    Patient Care: This research provides evidence for the safety of nanoparticle mediated thermoablation in the treatment of metastatic spine disease. Our research will support the translation of this treatment modality to human patients.

    Learning Objectives: By the conclusion of this session, participants should be able to 1) describe the importance of improved animal models for metastatic disease, 2) Discuss in small groups the utility of thermoablation in spine tumors and 3) identify nanoparticle mediated therapy as an effective treatment for metastatic spine tumors.

    References: 1. Sciubba DM, Gokaslan ZL: Diagnosis and management of metastatic spine disease. Surg Oncol 15:141-151, 2006 2. Sciubba DM, Petteys RJ, Dekutoski MB, Fisher CG, Fehlings MG, Ondra SL, et al: Diagnosis and management of metastatic spine disease J Neurosurg Spine 13:94-108, 2010 3. Hildebrandt B, Wust P, Ahlers O, Dieing A, Sreenivasa G, Kerner T, et al: The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol 43:33-56, 2002 4. Hilger I, Hergt R, Kaiser WA: Use of magnetic nanoparticle heating in the treatment of breast cancer. IEE Proc Nanobiotechnol 152:33-39, 2005

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