Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease: Laboratory investigation

Patricia L. Zadnik, Camilo A. Molina, Rachel Sarabia Estrada, Mari L. Groves, Michele Wabler, Jana Mihalic, Edward F. McCarthy, Ziya L. Gokaslan, Robert Ivkov, Daniel M. Sciubba

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)740-750
Number of pages11
JournalJournal of Neurosurgery: Spine
Volume20
Issue number6
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Nanoparticles
Heating
Spine
Magnetic Fields
Neoplasms
Fever
Temperature
Mass Spectrometry
Animal Care Committees
Inbred F344 Rats
Tissue Distribution
Palliative Care
Starch
Spinal Cord
Suspensions
Adenocarcinoma
Breast
Necrosis
Staining and Labeling
Breast Neoplasms

Keywords

  • Hyperthermia
  • Iron oxide nanoparticles
  • Magnetic nanoparticles
  • Oncology
  • Rat
  • Spine
  • Tumor

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Neurology

Cite this

Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease : Laboratory investigation. / Zadnik, Patricia L.; Molina, Camilo A.; Sarabia Estrada, Rachel; Groves, Mari L.; Wabler, Michele; Mihalic, Jana; McCarthy, Edward F.; Gokaslan, Ziya L.; Ivkov, Robert; Sciubba, Daniel M.

In: Journal of Neurosurgery: Spine, Vol. 20, No. 6, 2014, p. 740-750.

Research output: Contribution to journalArticle

Zadnik, Patricia L. ; Molina, Camilo A. ; Sarabia Estrada, Rachel ; Groves, Mari L. ; Wabler, Michele ; Mihalic, Jana ; McCarthy, Edward F. ; Gokaslan, Ziya L. ; Ivkov, Robert ; Sciubba, Daniel M. / Characterization of intratumor magnetic nanoparticle distribution and heating in a rat model of metastatic spine disease : Laboratory investigation. In: Journal of Neurosurgery: Spine. 2014 ; Vol. 20, No. 6. pp. 740-750.
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abstract = "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.",
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author = "Zadnik, {Patricia L.} and Molina, {Camilo A.} and {Sarabia Estrada}, Rachel and Groves, {Mari L.} and Michele Wabler and Jana Mihalic and McCarthy, {Edward F.} and Gokaslan, {Ziya L.} and Robert Ivkov and Sciubba, {Daniel M.}",
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AU - Zadnik, Patricia L.

AU - Molina, Camilo A.

AU - Sarabia Estrada, Rachel

AU - Groves, Mari L.

AU - Wabler, Michele

AU - Mihalic, Jana

AU - McCarthy, Edward F.

AU - Gokaslan, Ziya L.

AU - Ivkov, Robert

AU - Sciubba, Daniel M.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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KW - Iron oxide nanoparticles

KW - Magnetic nanoparticles

KW - Oncology

KW - Rat

KW - Spine

KW - Tumor

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