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

Hyunki Kim, Karri D. Folks, Lingling Guo, Jeffery C. Sellers, Naomi S. Fineberg, Cecil R. Stockard, William E. Grizzle, Donald J. Buchsbaum, Desiree E. Morgan, James F. George, Kurt R. Zinn

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n 5 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.

Original languageEnglish
Pages (from-to)153-167
Number of pages15
JournalMolecular Imaging
Volume10
Issue number3
DOIs
StatePublished - Jun 2011
Externally publishedYes

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