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

Barbara M. Grüner; Isabel Winkelmann; Annette Feuchtinger; Na Sun; Benjamin Balluff; Nicole Teichmann; Alexander Herner; Evdokia Kalideris; Katja Steiger; Rickmer Braren; Michaela Aichler; Irene Esposito; Roland M. Schmid; Axel Walch; Jens T. Siveke

doi:10.1158/1535-7163.MCT-15-0165

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

Barbara M. Grüner, Isabel Winkelmann, Annette Feuchtinger, Na Sun, Benjamin Balluff, Nicole Teichmann, Alexander Herner, Evdokia Kalideris, Katja Steiger, Rickmer Braren, Michaela Aichler, Irene Esposito, Roland M. Schmid, Axel Walch, Jens T. Siveke

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. The aim of this study was to investigate the emerging technology of matrixassisted 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. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P = 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate 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 of compounds in a preclinical setting and support drug imaging- based translational approaches.

Original language	English
Pages (from-to)	1145-1152
Number of pages	8
Journal	Molecular Cancer Therapeutics
Volume	15
Issue number	5
DOIs	https://doi.org/10.1158/1535-7163.MCT-15-0165
State	Published - May 2016

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10.1158/1535-7163.MCT-15-0165

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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., & Siveke, J. T. (2016). Modeling therapy response and spatial tissue distribution of erlotinib in pancreatic cancer. Molecular Cancer Therapeutics, 15(5), 1145-1152. https://doi.org/10.1158/1535-7163.MCT-15-0165

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title = "Modeling therapy response and spatial tissue distribution of erlotinib in pancreatic cancer",

abstract = "Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. The aim of this study was to investigate the emerging technology of matrixassisted 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. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P = 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate 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 of compounds in a preclinical setting and support drug imaging- based translational approaches.",

author = "Gr{\"u}ner, {Barbara M.} and Isabel Winkelmann and Annette Feuchtinger and Na Sun and Benjamin Balluff and Nicole Teichmann and Alexander Herner and Evdokia Kalideris and Katja Steiger and Rickmer Braren and Michaela Aichler and Irene Esposito and Schmid, {Roland M.} and Axel Walch and Siveke, {Jens T.}",

note = "Publisher Copyright: {\textcopyright} 2016 AACR.",

year = "2016",

month = may,

doi = "10.1158/1535-7163.MCT-15-0165",

language = "English",

volume = "15",

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journal = "Molecular Cancer Therapeutics",

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publisher = "American Association for Cancer Research Inc.",

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Grüner, BM, Winkelmann, I, Feuchtinger, A, Sun, N, Balluff, B, Teichmann, N, Herner, A, Kalideris, E, Steiger, K, Braren, R, Aichler, M, Esposito, I, Schmid, RM, Walch, A & Siveke, JT 2016, 'Modeling therapy response and spatial tissue distribution of erlotinib in pancreatic cancer', Molecular Cancer Therapeutics, vol. 15, no. 5, pp. 1145-1152. https://doi.org/10.1158/1535-7163.MCT-15-0165

TY - JOUR

T1 - Modeling therapy response and spatial tissue distribution of erlotinib in pancreatic cancer

AU - Grüner, Barbara M.

AU - Winkelmann, Isabel

AU - Feuchtinger, Annette

AU - Sun, Na

AU - Balluff, Benjamin

AU - Teichmann, Nicole

AU - Herner, Alexander

AU - Kalideris, Evdokia

AU - Steiger, Katja

AU - Braren, Rickmer

AU - Aichler, Michaela

AU - Esposito, Irene

AU - Schmid, Roland M.

AU - Walch, Axel

AU - Siveke, Jens T.

PY - 2016/5

Y1 - 2016/5

N2 - Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. The aim of this study was to investigate the emerging technology of matrixassisted 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. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P = 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate 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 of compounds in a preclinical setting and support drug imaging- based translational approaches.

AB - Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. The aim of this study was to investigate the emerging technology of matrixassisted 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. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P = 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate 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 of compounds in a preclinical setting and support drug imaging- based translational approaches.

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U2 - 10.1158/1535-7163.MCT-15-0165

DO - 10.1158/1535-7163.MCT-15-0165

M3 - Article

C2 - 26823494

AN - SCOPUS:84971422053

SN - 1535-7163

VL - 15

SP - 1145

EP - 1152

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

IS - 5

ER -

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

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