Distribution of gemcitabine is nearly homogenous in two orthotopic murine models of pancreatic cancer Journal Article


Authors: Kramer, R. M.; Russell, J.; Humm, J. L.
Article Title: Distribution of gemcitabine is nearly homogenous in two orthotopic murine models of pancreatic cancer
Abstract: Pancreatic cancer is one of the leading causes of cancer-related death in the United States. Gemcitabine is a common treatment, but response rates are low, perhaps due in part to tumor hypoxia. We utilized 14C-labeled gemcitabine to map distribution of the drug with respect to perfused and hypoxic regions of the tumor microenvironment in two orthotopic xenograft models of pancreatic cancer. There was only a slight reduction in gemcitabine in hypoxic areas, with ∼78% of the drug present in hypoxic compared to perfused areas. In addition, only a 4% reduction in gemcitabine was measured at >100μm from perfused blood vessels. Thus, despite significant areas of hypoxia in these tumors, gemcitabine distribution is relatively homogenous. Ours is the first study to directly measure gemcitabine distribution within tumor tissue, demonstrating that in these models, tumor tissue does not represent a barrier to gemcitabine penetration. © Copyright 2015, Mary Ann Liebert, Inc. 2015.
Keywords: controlled study; nonhuman; gemcitabine; pancreas cancer; mouse; animal tissue; image analysis; animal experiment; animal model; drug resistance; hypoxia; drug distribution; isotope labeling; autoradiography; click chemistry; orthotopic; perfusion; tumor microenvironment; pancreatic tumor; hypoxic cell; female; priority journal; article
Journal Title: Cancer Biotherapy and Radiopharmaceuticals
Volume: 30
Issue: 7
ISSN: 1084-9785
Publisher: Mary Ann Liebert, Inc  
Date Published: 2015-09-09
Start Page: 299
End Page: 304
Language: English
DOI: 10.1089/cbr.2015.1869
PROVIDER: scopus
PUBMED: 26203552
PMCID: PMC4696432
DOI/URL:
Notes: Export Date: 2 October 2015 -- Source: Scopus
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  1. John Laurence Humm
    434 Humm
  2. James Russell
    41 Russell
  3. Robin Marie Kramer
    3 Kramer