title: Early therapy evaluation of combined cetuximab and irinotecan in orthotopic pancreatic tumor xenografts by dynamic contrast-enhanced magnetic resonance imaging.
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.
authors.affiliation: Departments of Radiology, Comprehensive Cancer Center, University of Alabama at Birmingham, AL 35294-0012, USA. Hyunki@uab.edu
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.forename: Karri D
authors.initials: KD
authors.lastname: Folks
authors.forename: Lingling
authors.initials: L
authors.lastname: Guo
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Sellers
authors.forename: Naomi S
authors.initials: NS
authors.lastname: Fineberg
authors.forename: Cecil R
authors.initials: CR
authors.lastname: Stockard
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.forename: Desiree E
authors.initials: DE
authors.lastname: Morgan
authors.forename: James F
authors.initials: JF
authors.lastname: George
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003287:Contrast Media; D006801:Humans; D000077146:Irinotecan; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin