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Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects.

Publication ,  Journal Article
Ponce, AM; Viglianti, BL; Yu, D; Yarmolenko, PS; Michelich, CR; Woo, J; Bally, MB; Dewhirst, MW
Published in: J Natl Cancer Inst
January 3, 2007

BACKGROUND: In preclinical studies, lysolipid-based temperature-sensitive liposomes (LTSLs) containing chemotherapy drugs administered in combination with local hyperthermia have been found to increase tumor drug concentrations and improve antitumor efficacy of the drugs. We used a novel magnetic resonance imaging (MRI) method to measure the temporal and spatial patterns of drug delivery in a rat fibrosarcoma model during treatment with LTSLs containing doxorubicin and an MRI contrast agent (manganese) (Dox/Mn-LTSLs) administered at different times with respect to hyperthermia. METHODS: Rats bearing 10- to 12-mm fibrosarcomas (n = 6-7 per group) were treated with Dox/Mn-LTSLs (at a dose of 5 mg doxorubicin/kg body weight) before and/or during 60 minutes of local tumor hyperthermia administered via a catheter inserted at the center of the tumor. Drug distribution was monitored continuously via MRI. Magnetic resonance changes were used to calculate intratumoral doxorubicin concentrations throughout treatment. Tumors were monitored until they reached five times their volume on the day of treatment or 60 days. Doxorubicin concentrations and times for tumors to reach five times their volume on the day of treatment were analyzed using the Kruskal-Wallis test and the Kaplan-Meier product-limit method, respectively. All statistical tests were two-sided. RESULTS: Administration of Dox/Mn-LTSLs before, during, and both before and during hyperthermia yielded central, peripheral, and uniform drug distributions, respectively. Doxorubicin accumulated more quickly and reached higher concentrations in the tumor when Dox/Mn-LTSLs were administered during hyperthermia than when administered before hyperthermia (rate: 9.8 versus 1.8 microg/min, difference = 8.0 microg/min, 95% confidence interval [CI] = 6.8 to 12.8 microg/min, P = .003; concentration: 15.1 versus 8.0 ng/mg, difference = 7.1 ng/mg, 95% CI = 3.6 to 10.6 ng/mg, P = .028). LTSL administered during hyperthermia also yielded the greatest antitumor effect, with a median time for tumors to reach five times their volume on the day of treatment of 34 days (95% CI = 30 days to infinity) compared with 18.5 days (95% CI = 16 to 23 days) for LTSL before hyperthermia and 22.5 days (95% CI = 15 to 25 days) for LTSL before and during hyperthermia. CONCLUSIONS: In this rat fibrosarcoma model, LTSLs were most effective when delivered during hyperthermia, which resulted in a peripheral drug distribution.

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Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

January 3, 2007

Volume

99

Issue

1

Start / End Page

53 / 63

Location

United States

Related Subject Headings

  • Time Factors
  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Manganese Compounds
  • Magnetic Resonance Imaging
  • Liposomes
  • Hyperthermia, Induced
  • Fibrosarcoma
  • Female
 

Citation

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MLA
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Ponce, A. M., Viglianti, B. L., Yu, D., Yarmolenko, P. S., Michelich, C. R., Woo, J., … Dewhirst, M. W. (2007). Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects. J Natl Cancer Inst, 99(1), 53–63. https://doi.org/10.1093/jnci/djk005
Ponce, Ana M., Benjamin L. Viglianti, Daohai Yu, Pavel S. Yarmolenko, Charles R. Michelich, Janet Woo, Marcel B. Bally, and Mark W. Dewhirst. “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects.J Natl Cancer Inst 99, no. 1 (January 3, 2007): 53–63. https://doi.org/10.1093/jnci/djk005.
Ponce AM, Viglianti BL, Yu D, Yarmolenko PS, Michelich CR, Woo J, et al. Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects. J Natl Cancer Inst. 2007 Jan 3;99(1):53–63.
Ponce, Ana M., et al. “Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects.J Natl Cancer Inst, vol. 99, no. 1, Jan. 2007, pp. 53–63. Pubmed, doi:10.1093/jnci/djk005.
Ponce AM, Viglianti BL, Yu D, Yarmolenko PS, Michelich CR, Woo J, Bally MB, Dewhirst MW. Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects. J Natl Cancer Inst. 2007 Jan 3;99(1):53–63.
Journal cover image

Published In

J Natl Cancer Inst

DOI

EISSN

1460-2105

Publication Date

January 3, 2007

Volume

99

Issue

1

Start / End Page

53 / 63

Location

United States

Related Subject Headings

  • Time Factors
  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Manganese Compounds
  • Magnetic Resonance Imaging
  • Liposomes
  • Hyperthermia, Induced
  • Fibrosarcoma
  • Female