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A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

Publication ,  Journal Article
Kleiter, MM; Yu, D; Mohammadian, LA; Niehaus, N; Spasojevic, I; Sanders, L; Viglianti, BL; Yarmolenko, PS; Hauck, M; Petry, NA; Wong, TZ ...
Published in: Clin Cancer Res
November 15, 2006

PURPOSE: A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)-labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. EXPERIMENTAL DESIGN: Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. RESULTS: Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. CONCLUSIONS: The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

Duke Scholars

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

November 15, 2006

Volume

12

Issue

22

Start / End Page

6800 / 6807

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Thigh
  • Technetium Tc 99m Exametazime
  • Rats
  • Radioactive Tracers
  • Oncology & Carcinogenesis
  • Liposomes
  • Hyperthermia, Induced
  • Fibrosarcoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kleiter, M. M., Yu, D., Mohammadian, L. A., Niehaus, N., Spasojevic, I., Sanders, L., … Thrall, D. E. (2006). A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation. Clin Cancer Res, 12(22), 6800–6807. https://doi.org/10.1158/1078-0432.CCR-06-0839
Kleiter, Miriam M., Daohai Yu, Lenore A. Mohammadian, Nelsen Niehaus, Ivan Spasojevic, Linda Sanders, Benjamin L. Viglianti, et al. “A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.Clin Cancer Res 12, no. 22 (November 15, 2006): 6800–6807. https://doi.org/10.1158/1078-0432.CCR-06-0839.
Kleiter MM, Yu D, Mohammadian LA, Niehaus N, Spasojevic I, Sanders L, et al. A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation. Clin Cancer Res. 2006 Nov 15;12(22):6800–7.
Kleiter, Miriam M., et al. “A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.Clin Cancer Res, vol. 12, no. 22, Nov. 2006, pp. 6800–07. Pubmed, doi:10.1158/1078-0432.CCR-06-0839.
Kleiter MM, Yu D, Mohammadian LA, Niehaus N, Spasojevic I, Sanders L, Viglianti BL, Yarmolenko PS, Hauck M, Petry NA, Wong TZ, Dewhirst MW, Thrall DE. A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation. Clin Cancer Res. 2006 Nov 15;12(22):6800–6807.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

November 15, 2006

Volume

12

Issue

22

Start / End Page

6800 / 6807

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Thigh
  • Technetium Tc 99m Exametazime
  • Rats
  • Radioactive Tracers
  • Oncology & Carcinogenesis
  • Liposomes
  • Hyperthermia, Induced
  • Fibrosarcoma