Early therapy evaluation of combined cetuximab and irinotecan in orthotopic pancreatic tumor xenografts by dynamic contrast-enhanced magnetic resonance imaging.

Academic Article

Abstract

  • Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n  =  6/group) of SCID mice bearing orthotopic pancreatic adenocarcinoma xenografts expressing luciferase were treated with phosphate-buffered saline, cetuximab, irinotecan, or cetuximab combined with irinotecan, respectively, twice weekly for 3 weeks. DCE-MRI was performed on days 0, 1, 2, and 3 after therapy initiation, whereas anatomic magnetic resonance imaging was performed on days 0, 1, 2, 3, 6, and 13. Bioluminescence imaging was performed on days 0 and 21. At day 21, all tumors were collected for further histologic analyses (Ki-67 and CD31 staining), whereas tumor dimensions were measured by calipers. The Ktrans values in the 0.5 mm-thick peripheral tumor region were calculated, and the changes in Ktrans during the 3 days posttherapy were compared to tumor volume changes, bioluminescent signal changes, and histologic findings. The Ktrans changes in the peripheral tumor region after 3 days of therapy were linearly correlated with 21-day decreases in tumor volume (p < .001), bioluminescent signal (p  =  .050), microvessel densities (p  =  .002), and proliferating cell densities (p  =  .001). This study supports the clinical use of DCE-MRI for pancreatic cancer patients for early assessment of an anti-epidermal growth factor receptor therapy combined with chemotherapy.
  • Published In

  • Molecular Imaging  Journal
  • Keywords

  • Animals, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Camptothecin, Cell Line, Tumor, Cetuximab, Contrast Media, Humans, Irinotecan, Magnetic Resonance Imaging, Mice, Mice, SCID, Pancreatic Neoplasms, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed, Tumor Burden, Xenograft Model Antitumor Assays
  • Author List

  • Kim H; Folks KD; Guo L; Sellers JC; Fineberg NS; Stockard CR; Grizzle WE; Buchsbaum DJ; Morgan DE; George JF
  • Start Page

  • 153
  • End Page

  • 167
  • Volume

  • 10
  • Issue

  • 3