Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer

Robert Ivkov, Sally J. DeNardo, Wolfgang Daum, Allan R. Foreman, Robert C. Goldstein, Valentin S. Nemkov, Gerald L. DeNardo

Research output: Contribution to journalArticle

Abstract

Objective: Magnetic nanoparticles conjugated to a monoclonal antibody can be i.v. injected to target cancer tissue and will rapidly heat when activated by an external alternating magnetic field (AMF). The result is necrosis of the microenvironment provided the concentration of particles and AMF amplitude are sufficient. High-amplitude AMF causes nonspecific heating in tissues through induced eddy currents, which must be minimized. In this study, application of high-amplitude, confined, pulsed AMF to a mouse model is explored with the goal to provide data for a concomitant efficacy study of heating i.v. injected magnetic nanoparticles. Methods: Thirty-seven female BALB/c athymic nude mice (5-8 weeks) were exposed to an AMF with frequency of 153 kHz, and amplitude (400-1,300 Oe), duration (1-20 minutes), duty (15-100%), and pulse ON time (2-1,200 seconds). Mice were placed in a water-cooled four-turn helical induction coil. Two additional mice, used as controls, were placed in the coil but received no AMF exposure. Tissue and core temperatures as the response were measured in situ and recorded at 1-second intervals. Results: No adverse effects were observed for AMF amplitudes of ≤700 Oe, even at continuous power application (100% duty) for up to 20 minutes. Mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury when the duty exceeded 50%. Conclusion: High-amplitude AMF (up to 1,300 Oe) was well tolerated provided the duty was adjusted to dissipate heat. Results presented suggest that further tissue temperature regulation can be achieved with suitable variations of pulse width for a given amplitude and duty combination. These results suggest that it is possible to apply high-amplitude AMF (>500 Oe) with pulsing for a time sufficient to treat cancer tissue in which magnetic nanoparticles have been embedded.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume11
Issue number19 II
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Fingerprint

Magnetic Fields
Nanoparticles
Hot Temperature
Neoplasms
Nude Mice
Heating
Temperature
Necrosis
Monoclonal Antibodies
Morbidity
Water
Wounds and Injuries

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer. / Ivkov, Robert; DeNardo, Sally J.; Daum, Wolfgang; Foreman, Allan R.; Goldstein, Robert C.; Nemkov, Valentin S.; DeNardo, Gerald L.

In: Clinical Cancer Research, Vol. 11, No. 19 II, 01.10.2005.

Research output: Contribution to journalArticle

Ivkov, Robert ; DeNardo, Sally J. ; Daum, Wolfgang ; Foreman, Allan R. ; Goldstein, Robert C. ; Nemkov, Valentin S. ; DeNardo, Gerald L. / Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 19 II.
@article{3ad34b3a99c349d7824f24d3e45d32b5,
title = "Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer",
abstract = "Objective: Magnetic nanoparticles conjugated to a monoclonal antibody can be i.v. injected to target cancer tissue and will rapidly heat when activated by an external alternating magnetic field (AMF). The result is necrosis of the microenvironment provided the concentration of particles and AMF amplitude are sufficient. High-amplitude AMF causes nonspecific heating in tissues through induced eddy currents, which must be minimized. In this study, application of high-amplitude, confined, pulsed AMF to a mouse model is explored with the goal to provide data for a concomitant efficacy study of heating i.v. injected magnetic nanoparticles. Methods: Thirty-seven female BALB/c athymic nude mice (5-8 weeks) were exposed to an AMF with frequency of 153 kHz, and amplitude (400-1,300 Oe), duration (1-20 minutes), duty (15-100{\%}), and pulse ON time (2-1,200 seconds). Mice were placed in a water-cooled four-turn helical induction coil. Two additional mice, used as controls, were placed in the coil but received no AMF exposure. Tissue and core temperatures as the response were measured in situ and recorded at 1-second intervals. Results: No adverse effects were observed for AMF amplitudes of ≤700 Oe, even at continuous power application (100{\%} duty) for up to 20 minutes. Mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury when the duty exceeded 50{\%}. Conclusion: High-amplitude AMF (up to 1,300 Oe) was well tolerated provided the duty was adjusted to dissipate heat. Results presented suggest that further tissue temperature regulation can be achieved with suitable variations of pulse width for a given amplitude and duty combination. These results suggest that it is possible to apply high-amplitude AMF (>500 Oe) with pulsing for a time sufficient to treat cancer tissue in which magnetic nanoparticles have been embedded.",
author = "Robert Ivkov and DeNardo, {Sally J.} and Wolfgang Daum and Foreman, {Allan R.} and Goldstein, {Robert C.} and Nemkov, {Valentin S.} and DeNardo, {Gerald L.}",
year = "2005",
month = "10",
day = "1",
doi = "10.1158/1078-0432.CCR-1004-0016",
language = "English (US)",
volume = "11",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "19 II",

}

TY - JOUR

T1 - Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer

AU - Ivkov, Robert

AU - DeNardo, Sally J.

AU - Daum, Wolfgang

AU - Foreman, Allan R.

AU - Goldstein, Robert C.

AU - Nemkov, Valentin S.

AU - DeNardo, Gerald L.

PY - 2005/10/1

Y1 - 2005/10/1

N2 - Objective: Magnetic nanoparticles conjugated to a monoclonal antibody can be i.v. injected to target cancer tissue and will rapidly heat when activated by an external alternating magnetic field (AMF). The result is necrosis of the microenvironment provided the concentration of particles and AMF amplitude are sufficient. High-amplitude AMF causes nonspecific heating in tissues through induced eddy currents, which must be minimized. In this study, application of high-amplitude, confined, pulsed AMF to a mouse model is explored with the goal to provide data for a concomitant efficacy study of heating i.v. injected magnetic nanoparticles. Methods: Thirty-seven female BALB/c athymic nude mice (5-8 weeks) were exposed to an AMF with frequency of 153 kHz, and amplitude (400-1,300 Oe), duration (1-20 minutes), duty (15-100%), and pulse ON time (2-1,200 seconds). Mice were placed in a water-cooled four-turn helical induction coil. Two additional mice, used as controls, were placed in the coil but received no AMF exposure. Tissue and core temperatures as the response were measured in situ and recorded at 1-second intervals. Results: No adverse effects were observed for AMF amplitudes of ≤700 Oe, even at continuous power application (100% duty) for up to 20 minutes. Mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury when the duty exceeded 50%. Conclusion: High-amplitude AMF (up to 1,300 Oe) was well tolerated provided the duty was adjusted to dissipate heat. Results presented suggest that further tissue temperature regulation can be achieved with suitable variations of pulse width for a given amplitude and duty combination. These results suggest that it is possible to apply high-amplitude AMF (>500 Oe) with pulsing for a time sufficient to treat cancer tissue in which magnetic nanoparticles have been embedded.

AB - Objective: Magnetic nanoparticles conjugated to a monoclonal antibody can be i.v. injected to target cancer tissue and will rapidly heat when activated by an external alternating magnetic field (AMF). The result is necrosis of the microenvironment provided the concentration of particles and AMF amplitude are sufficient. High-amplitude AMF causes nonspecific heating in tissues through induced eddy currents, which must be minimized. In this study, application of high-amplitude, confined, pulsed AMF to a mouse model is explored with the goal to provide data for a concomitant efficacy study of heating i.v. injected magnetic nanoparticles. Methods: Thirty-seven female BALB/c athymic nude mice (5-8 weeks) were exposed to an AMF with frequency of 153 kHz, and amplitude (400-1,300 Oe), duration (1-20 minutes), duty (15-100%), and pulse ON time (2-1,200 seconds). Mice were placed in a water-cooled four-turn helical induction coil. Two additional mice, used as controls, were placed in the coil but received no AMF exposure. Tissue and core temperatures as the response were measured in situ and recorded at 1-second intervals. Results: No adverse effects were observed for AMF amplitudes of ≤700 Oe, even at continuous power application (100% duty) for up to 20 minutes. Mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury when the duty exceeded 50%. Conclusion: High-amplitude AMF (up to 1,300 Oe) was well tolerated provided the duty was adjusted to dissipate heat. Results presented suggest that further tissue temperature regulation can be achieved with suitable variations of pulse width for a given amplitude and duty combination. These results suggest that it is possible to apply high-amplitude AMF (>500 Oe) with pulsing for a time sufficient to treat cancer tissue in which magnetic nanoparticles have been embedded.

UR - http://www.scopus.com/inward/record.url?scp=26444526995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26444526995&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-1004-0016

DO - 10.1158/1078-0432.CCR-1004-0016

M3 - Article

C2 - 16203808

AN - SCOPUS:26444526995

VL - 11

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 19 II

ER -