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Grüner, B.M.* ; Winkelmann, I. ; Feuchtinger, A. ; Sun, N. ; Balluff, B.* ; Teichmann, N.* ; Herner, A.* ; Kalideris, E.* ; Steiger, K.* ; Braren, R.* ; Aichler, M. ; Esposito, I.* ; Schmid, R.M.* ; Walch, A.K. ; Siveke, J.T.*

Modeling therapy response and spatial tissue distribution of erlotinib in pancreatic cancer.

Mol. Cancer Ther. 15, 1145-1152 (2016)
Verlagsversion Postprint DOI PMC
Open Access Green
Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. Aim of this study was to investigate the emerging technology of matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) as a powerful tool to study drug delivery and spatial tissue distribution in PDAC. We utilized an established genetically engineered mouse model of spontaneous PDAC to examine the distribution of the small molecule inhibitor erlotinib in healthy pancreas and PDAC. MALDI IMS was utilized on sections of single-dose or long-term-treated mice to measure drug tissue distribution. Histological and statistical analyses were performed to correlate morphology, drug distribution and survival. We found that erlotinib levels were significantly lower in PDAC compared to healthy tissue (p = 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histological tumor grade but both with the percentage of atypical glands in the cancer (p = 0.021, rs = 0.59) and the level of erlotinib in those atypical glands (p = 0.019, rs = 0.60). The results of this pilot study present MALDI IMS as a reliable technology to study drug delivery and spatial distribution compounds in a preclinical setting and supports drug imaging-based translational approaches.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Imaging Mass-spectrometry; Drug Distributions; Mouse Model; Sections; Biology; Mice; Adenocarcinoma; Gemcitabine; Receptor; Cells
ISSN (print) / ISBN 1535-7163
e-ISSN 1538-8514
Zeitschrift Molecular Cancer Therapeutics
Quellenangaben Band: 15, Heft: 5, Seiten: 1145-1152 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)