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Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents

Publication ,  Conference
Whitley, MJ; Cardona, DM; Blazer, DG; Hwang, S; Greenup, RA; Mosca, PJ; Cahill, J; Mito, JK; Cuneo, KC; Larrier, N; O'Reilly, E; Spasojevic, I ...
Published in: Cancer Research
August 1, 2015

Intra-operative detection of residual cancer in the tumor bed can be used to decrease the risk of a positive surgical margin, reduce the rate of re-excision, and tailor adjuvant therapy. LUM015 is a pegylated protease-activated imaging agent containing a near infrared fluorophore and quencher attached by a polypeptide linker. Using mouse models of soft tissue sarcoma (STS), we showed that LUM015 selectively localizes to the tumor and upon cleavage of the linker by proteases in the tissue, the quencher is released, allowing fluorescence to be detected.We recently completed a phase I clinical trial to test the safety of LUM015 in human patients with cancer. This open-label nonrandomized trial compared 3 dose cohorts (0.5, 1.0, and 1.5 mg/kg) of LUM015 in order to determine a safe dose of LUM015 that labels tumors in humans. A total of 15 subjects, 12 with STS and 3 with breast cancer, received IV LUM015 prior to surgical resection without any adverse pharmacological activity (APA). Quantitative fluorescence imaging of the resected tissues revealed that tumor fluorescence was significantly higher than corresponding normal tissue from the same patient (p<0.0001) with a mean tumor to normal fluorescence ratio of 5.4. Furthermore, within the study population, the distribution of tumor fluorescence values was significantly higher than those recorded for fat or muscle (p<0.009).We conducted comparative analyses of LUM015 pharmacodynamics in mouse and human subjects showing that biodistribution into tumors and activation by proteases is conserved across species. These studies revealed the presence of a novel, small molecule metabolite that correlates strongly with tissue fluorescence. Additional in vivo studies in mice and in vitro studies with mouse and human tissues showed that LUM015 is selectively distributed to and accumulates in tumors to result in increased fluorescence when compared to normal tissues.Citation Format: Melodi J. Whitley, Diana M. Cardona, Dan G. Blazer, Shelley Hwang, Rachel A. Greenup, Paul J. Mosca, Joan Cahill, Jeffrey K. Mito, Kyle C. Cuneo, Nicole Larrier, Erin O'Reilly, Ivan Spasojevic, Richard F. Riedel, William C. Eward, Linda G. Griffith, Moungi G. Bawendi, Jorge Ferrer, David B. Strasfeld, W. David Lee, Brian Brigman, David G. Kirsch. Intraoperative molecular imaging with protease-activated fluorescent imaging agents. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY36-03. doi:10.1158/1538-7445.AM2015-SY36-03

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

August 1, 2015

Volume

75

Issue

15_Supplement

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Whitley, M. J., Cardona, D. M., Blazer, D. G., Hwang, S., Greenup, R. A., Mosca, P. J., … Kirsch, D. G. (2015). Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents. In Cancer Research (Vol. 75). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.am2015-sy36-03
Whitley, Melodi J., Diana M. Cardona, Dan G. Blazer, Shelley Hwang, Rachel A. Greenup, Paul J. Mosca, Joan Cahill, et al. “Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents.” In Cancer Research, Vol. 75. American Association for Cancer Research (AACR), 2015. https://doi.org/10.1158/1538-7445.am2015-sy36-03.
Whitley MJ, Cardona DM, Blazer DG, Hwang S, Greenup RA, Mosca PJ, et al. Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents. In: Cancer Research. American Association for Cancer Research (AACR); 2015.
Whitley, Melodi J., et al. “Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents.” Cancer Research, vol. 75, no. 15_Supplement, American Association for Cancer Research (AACR), 2015. Crossref, doi:10.1158/1538-7445.am2015-sy36-03.
Whitley MJ, Cardona DM, Blazer DG, Hwang S, Greenup RA, Mosca PJ, Cahill J, Mito JK, Cuneo KC, Larrier N, O’Reilly E, Spasojevic I, Riedel RF, Eward WC, Griffith LG, Bawendi MG, Ferrer J, Strasfeld DB, Lee WD, Brigman B, Kirsch DG. Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents. Cancer Research. American Association for Cancer Research (AACR); 2015.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

August 1, 2015

Volume

75

Issue

15_Supplement

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis