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Journal of Biomedical Optics

Multiphoton fluorescence lifetime imaging of chemotherapy distribution in solid tumors
Author(s): Marjorie Carlson; Adrienne L. Watson; Leah Anderson; David A. Largaespada; Paolo P. Provenzano
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Paper Abstract

Doxorubicin is a commonly used chemotherapeutic employed to treat multiple human cancers, including numerous sarcomas and carcinomas. Furthermore, doxorubicin possesses strong fluorescent properties that make it an ideal reagent for modeling drug delivery by examining its distribution in cells and tissues. However, while doxorubicin fluorescence and lifetime have been imaged in live tissue, its behavior in archival samples that frequently result from drug and treatment studies in human and animal patients, and murine models of human cancer, has to date been largely unexplored. Here, we demonstrate imaging of doxorubicin intensity and lifetimes in archival formalin-fixed paraffin-embedded sections from mouse models of human cancer with multiphoton excitation and multiphoton fluorescence lifetime imaging microscopy (FLIM). Multiphoton excitation imaging reveals robust doxorubicin emission in tissue sections and captures spatial heterogeneity in cells and tissues. However, quantifying the amount of doxorubicin signal in distinct cell compartments, particularly the nucleus, often remains challenging due to strong signals in multiple compartments. The addition of FLIM analysis to display the spatial distribution of excited state lifetimes clearly distinguishes between signals in distinct compartments such as the cell nuclei versus cytoplasm and allows for quantification of doxorubicin signal in each compartment. Furthermore, we observed a shift in lifetime values in the nuclei of transformed cells versus nontransformed cells, suggesting a possible diagnostic role for doxorubicin lifetime imaging to distinguish normal versus transformed cells. Thus, data here demonstrate that multiphoton FLIM is a highly sensitive platform for imaging doxorubicin distribution in normal and diseased archival tissues.

Paper Details

Date Published: 29 November 2017
PDF: 9 pages
J. Biomed. Opt. 22(11) 116010 doi: 10.1117/1.JBO.22.11.116010
Published in: Journal of Biomedical Optics Volume 22, Issue 11
Show Author Affiliations
Marjorie Carlson, Univ. of Minnesota, Twin Cities (United States)
Physical Sciences in Oncology Ctr., Univ. of Minnesota, Twin Cities (United States)
Adrienne L. Watson, Masonic Cancer Ctr., Univ. of Minnesota (United States)
Leah Anderson, Masonic Cancer Ctr., Univ. of Minnesota (United States)
David A. Largaespada, Masonic Cancer Ctr., Univ. of Minnesota (United States)
Paolo P. Provenzano, Univ. of Minnesota, Twin Cities (United States)
Physical Sciences in Oncology Ctr., Univ. of Minnesota (United States)
Masonic Cancer Ctr., Univ. of Minnesota (United States)


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