Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease.
OBJECT
The goal of this study was to optimize local delivery of magnetic nanoparticles in a rat model of metastatic breast cancer in the spine for tumor hyperthermia while minimizing systemic exposure.


METHODS
A syngeneic mammary adenocarcinoma was implanted into the L-6 vertebral body of 69 female Fischer rats. Suspensions of 100-nm starch-coated iron oxide magnetic nanoparticles (micromod Partikeltechnologie GmbH) were injected into tumors 9 or 13 days after implantation. For nanoparticle distribution studies, tissues were harvested from a cohort of 36 rats, and inductively coupled plasma mass spectrometry and histopathological studies with Prussian blue staining were used to analyze the samples. Intratumor heating was tested in 4 anesthetized animals with a 20-minute exposure to an alternating magnetic field (AMF) at a frequency of 150 kHz and an amplitude of 48 kA/m or 63.3 kA/m. Intratumor and rectal temperatures were measured, and functional assessments of AMF-exposed animals and histopathological studies of heated tumor samples were examined. Rectal temperatures alone were tested in a cohort of 29 rats during AMF exposure with or without nanoparticle administration. Animal studies were completed in accordance with the protocols of the University Animal Care and Use Committee.


RESULTS
Nanoparticles remained within the tumor mass within 3 hours of injection and migrated into the bone at 6, 12, and 24 hours. Subarachnoid accumulation of nanoparticles was noted at 48 hours. No evidence of lymphoreticular nanoparticle exposure was found on histological investigation or via inductively coupled plasma mass spectrometry. The mean intratumor temperatures were 43.2°C and 40.6°C on exposure to 63.3 kA/m and 48 kA/m, respectively, with histological evidence of necrosis. All animals were ambulatory at 24 hours after treatment with no evidence of neurological dysfunction.


CONCLUSIONS
Locally delivered magnetic nanoparticles activated by an AMF can generate hyperthermia in spinal tumors without accumulating in the lymphoreticular system and without damaging the spinal cord, thereby limiting neurological dysfunction and minimizing systemic exposure. Magnetic nanoparticle hyperthermia may be a viable option for palliative therapy of spinal tumors.
['Zadnik|Patricia L|PL|', 'Molina|Camilo A|CA|', 'Sarabia-Estrada|Rachel|R|', 'Groves|Mari L|ML|', 'Wabler|Michele|M|', 'Mihalic|Jana|J|', 'McCarthy|Edward F|EF|', 'Gokaslan|Ziya L|ZL|', 'Ivkov|Robert|R|', 'Sciubba|Daniel|D|']
D000230:Adenocarcinoma D000818:Animals D045744:Cell Line, Tumor D004195:Disease Models, Animal D005260:Female D006979:Hyperthermia, Induced D058185:Magnetite Nanoparticles D008325:Mammary Neoplasms, Experimental D011897:Random Allocation D051381:Rats D011916:Rats, Inbred F344 D013054:Spectrophotometry, Atomic D013125:Spinal Neoplasms D013535:Suspensions
magnetic nanoparticles rat spine tumor hyperthermia AMF = alternating magnetic field BNF = Bionized Nanoferrite ICP-MS = inductively coupled plasma mass spectrometry PB = Prussian blue SLP = specific loss power VB = vertebral body iron oxide nanoparticles oncology