Rofo 2013; 185 - VO105_I_7
DOI: 10.1055/s-0033-1346234

ADC as therapy response marker for pancreatic ductal adenocarcinoma in genetically engineered mice

M Trajkovic-Arsic 1, I Heid 2, I Esposito 3, K Steiger 3, N Teichmann 4, A Steingötter 5, D Menne 6, A Scholz 7, EJ Rummeny 2, J Siveke 4, R Braren 2
  • 12. Medizinische Klinik, Gastroenterologie, München
  • 2Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, München
  • 3Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, München
  • 42nd Department of Internal Medicine, Klinikum rechts der Isar, Technische Universität München, München
  • 5Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich
  • 6Menne Biomed Consulting, Tübingen
  • 7Bayer Schering Pharma, Berlin

Ziele: High chemoresistance due to tumor heterogeneity is a hallmark of pancreatic ductal adenocarcinoma (PDAC). Non-invasive imaging parameters that allow early identification of individual therapy responsive tumors or tumor subregions and facilitate therapy choice are missing. Here we report on Apparent Diffusion Coefficient (ADC) as early therapy response marker in genetically engineered mouse models of pancreatic cancer. Methode: Ptf1a+/Cre;Kras+/LSL-G12D;p53LoxP/LoxP mice develop moderately differentiated PDAC that recapitulates well stroma rich human PDAC. Two chemotherapies were applied: standard of care Gemcitabine (120 mg/gr BW, 4 doses in 2 weeks) and a newly developed MAP kinase-targeting agent BAY 86 – 9766 (daily 25 mg/gr BW). Therapy induced changes in tumor growth kinetics and tissue composition were followed by T2w- and DW-MRI on a Philips Achieva 1,5T clinical scanner. Histological evaluation was used as gold standard. Ergebnis: BAY86 – 9766 treatment induced a highly significant increase in mean ADC values (0,98 ± 0,1 to 1,1 ± 0,1) already at 24 hours, followed by a nearly complete loss of tumor mass at day 5 and a significant survival benefit (BAY 86 – 9766 81 vs. 61 days vehicle). In contrast, only single Gemcitabine treated animals demonstrated an increase in tumor ADC value, which corresponded to an increase in survival, whereas median survival (Gemcitabine 69,5 vs. 62,5 days vehicle) did not increase. Translational value of this finding is confirmed in human patients, with an early (i.e. 2 – 4 week) increase in ADC value identifying tumor volume response at 3 month. Schlussfolgerung: In conclusion, we suggest ADC value as a therapy response predictor for murine and human PDAC.

Korrespondierender Autor: Trajkovic-Arsic M

2. Medizinische Klinik, Gastroenterologie, Ismaninger Str. 22, 81675 München

E-Mail: trajkovicmarija1@googlemail.com

Tumor heterogeneity - Pancreatic Cancer - Diffusion Weighted MRI - Apparent Diffusion Coefficient