Molecular Imaging and Biology

, Volume 16, Issue 1, pp 85–94 | Cite as

Antagonistic Effects of Anti-EMMPRIN Antibody When Combined with Chemotherapy Against Hypovascular Pancreatic Cancers

  • Hyunki Kim
  • Christopher J. Rigell
  • Guihua Zhai
  • S. Kyle Lee
  • Sharon L. Samuel
  • Amber Martin
  • Heidi R. Umphrey
  • Cecil R. Stockard
  • T. Mark Beasley
  • Donald J. Buchsbaum
  • Long Shan Li
  • David A. Boothman
  • Kurt R. Zinn
Research Article

Abstract

Purpose

To examine the antagonistic effects of anti-extracellular matrix metalloprotease inducer (anti-EMMPRIN) antibody when combined with chemotherapy using a hypovascular pancreatic tumor model.

Procedures

Severely compromised immunodeficient mice bearing orthotopic MIA PaCa-2 tumors were used (five to six animals per group). Dynamic contrast-enhanced magnetic resonance imaging was used to examine the relationship between tumor vascularity and size. Therapy was initiated when tumors were hypovascular. Treatments included: (1) gemcitabine alone, (2) anti-EMMPRIN antibody alone, and (3) combination, each for 2 weeks. Additionally, another treatment arm included β-lapachone, an NAD(P)H/quinone 1 (NQO1) bioactivated agent. 18F-fluoro-D-glucose-positron emission tomography/computed tomography imaging was used weekly to monitor therapeutic effects.

Results

Gemcitabine or anti-EMMPRIN monotherapy significantly delayed tumor growth, but the combination therapy showed an antagonistic effect. Similarly, tumor growth was significantly suppressed by β-lapachone alone, and additive effects were noted when combined with gemcitabine, but the therapeutic efficacy was reduced when anti-EMMPRIN antibody was added.

Conclusions

Anti-EMMPRIN antibody with chemotherapy in hypovascular tumors results in antagonistic effects.

Key words

Pancreatic cancer EMMPRIN β-Lapachone Gemcitabine DCE-MRI FDG-PET/CT 

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Copyright information

© World Molecular Imaging Society 2013

Authors and Affiliations

  • Hyunki Kim
    • 1
    • 2
    • 6
    • 10
  • Christopher J. Rigell
    • 3
  • Guihua Zhai
    • 1
  • S. Kyle Lee
    • 3
  • Sharon L. Samuel
    • 1
  • Amber Martin
    • 1
  • Heidi R. Umphrey
    • 1
    • 6
  • Cecil R. Stockard
    • 6
  • T. Mark Beasley
    • 4
  • Donald J. Buchsbaum
    • 5
  • Long Shan Li
    • 7
    • 8
    • 9
  • David A. Boothman
    • 7
    • 8
    • 9
  • Kurt R. Zinn
    • 1
    • 3
    • 6
  1. 1.Department of RadiologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Biomedical EngineeringUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of BiostatisticsUniversity of Alabama at BirminghamBirminghamUSA
  5. 5.Department of Radiation OncologyUniversity of Alabama at BirminghamBirminghamUSA
  6. 6.Comprehensive Cancer CenterUniversity of Alabama at BirminghamBirminghamUSA
  7. 7.Department of PharmacologyUniversity of Texas Southwestern Medical CenterDallasUSA
  8. 8.Department of Radiation OncologyUniversity of Texas Southwestern Medical CenterDallasUSA
  9. 9.Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  10. 10.BirminghamUSA

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