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Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents.

Publication ,  Journal Article
Cuneo, KC; Mito, JK; Javid, MP; Ferrer, JM; Kim, Y; Lee, WD; Bawendi, MG; Brigman, BE; Kirsch, DG
Published in: Int J Radiat Oncol Biol Phys
May 1, 2013

PURPOSE: Cathepsin-activated fluorescent probes can detect tumors in mice and in canine patients. We previously showed that these probes can detect microscopic residual sarcoma in the tumor bed of mice during gross total resection. Many patients with soft tissue sarcoma (STS) and other tumors undergo radiation therapy (RT) before surgery. This study assesses the effect of RT on the ability of cathepsin-activated probes to differentiate between normal and cancerous tissue. METHODS AND MATERIALS: A genetically engineered mouse model of STS was used to generate primary hind limb sarcomas that were treated with hypofractionated RT. Mice were injected intravenously with cathepsin-activated fluorescent probes, and various tissues, including the tumor, were imaged using a hand-held imaging device. Resected tumor and normal muscle samples were harvested to assess cathepsin expression by Western blot. Uptake of activated probe was analyzed by flow cytometry and confocal microscopy. Parallel in vitro studies using mouse sarcoma cells were performed. RESULTS: RT of primary STS in mice and mouse sarcoma cell lines caused no change in probe activation or cathepsin protease expression. Increasing radiation dose resulted in an upward trend in probe activation. Flow cytometry and immunofluorescence showed that a substantial proportion of probe-labeled cells were CD11b-positive tumor-associated immune cells. CONCLUSIONS: In this primary murine model of STS, RT did not affect the ability of cathepsin-activated probes to differentiate between tumor and normal muscle. Cathepsin-activated probes labeled tumor cells and tumor-associated macrophages. Our results suggest that it would be feasible to include patients who have received preoperative RT in clinical studies evaluating cathepsin-activated imaging probes.

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Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

May 1, 2013

Volume

86

Issue

1

Start / End Page

136 / 142

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Tissue Distribution
  • Sarcoma, Experimental
  • Oncology & Carcinogenesis
  • Muscle, Skeletal
  • Microscopy, Confocal
  • Mice
  • Hindlimb
  • Fluorescent Dyes
  • Flow Cytometry
 

Citation

APA
Chicago
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MLA
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Cuneo, K. C., Mito, J. K., Javid, M. P., Ferrer, J. M., Kim, Y., Lee, W. D., … Kirsch, D. G. (2013). Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents. Int J Radiat Oncol Biol Phys, 86(1), 136–142. https://doi.org/10.1016/j.ijrobp.2012.12.007
Cuneo, Kyle C., Jeffrey K. Mito, Melodi P. Javid, Jorge M. Ferrer, Yongbaek Kim, W David Lee, Moungi G. Bawendi, Brian E. Brigman, and David G. Kirsch. “Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents.Int J Radiat Oncol Biol Phys 86, no. 1 (May 1, 2013): 136–42. https://doi.org/10.1016/j.ijrobp.2012.12.007.
Cuneo KC, Mito JK, Javid MP, Ferrer JM, Kim Y, Lee WD, et al. Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents. Int J Radiat Oncol Biol Phys. 2013 May 1;86(1):136–42.
Cuneo, Kyle C., et al. “Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents.Int J Radiat Oncol Biol Phys, vol. 86, no. 1, May 2013, pp. 136–42. Pubmed, doi:10.1016/j.ijrobp.2012.12.007.
Cuneo KC, Mito JK, Javid MP, Ferrer JM, Kim Y, Lee WD, Bawendi MG, Brigman BE, Kirsch DG. Imaging primary mouse sarcomas after radiation therapy using cathepsin-activatable fluorescent imaging agents. Int J Radiat Oncol Biol Phys. 2013 May 1;86(1):136–142.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

May 1, 2013

Volume

86

Issue

1

Start / End Page

136 / 142

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Tissue Distribution
  • Sarcoma, Experimental
  • Oncology & Carcinogenesis
  • Muscle, Skeletal
  • Microscopy, Confocal
  • Mice
  • Hindlimb
  • Fluorescent Dyes
  • Flow Cytometry