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Immunology

Abstract 1795: Therapy assessment of a novel anti-EMMPRIN antibody and gemcitabine in an orthotopic pancreatic-tumor murine model by FDG PET/CT imaging

Nemil Shah, Guihua Zhai, Joseph Knowles, Cecil Stockard, William Grizzle, Naomi Fineberg, Tong Zhou, Kurt Zinn, Eben Rosenthal and Hyunki Kim
Nemil Shah
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Guihua Zhai
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Joseph Knowles
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Cecil Stockard
1Univ. of Alabama at Birmingham, Birmingham, AL.
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William Grizzle
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Naomi Fineberg
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Tong Zhou
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Kurt Zinn
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Eben Rosenthal
1Univ. of Alabama at Birmingham, Birmingham, AL.
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Hyunki Kim
1Univ. of Alabama at Birmingham, Birmingham, AL.
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DOI: 10.1158/1538-7445.AM2011-1795 Published April 2011
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Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL

Abstract

Purpose: To evaluate a novel monoclonal antibody targeting human EMMPRIN with/without gemcitabine in an orthotopic pancreatic-tumor model by sequential 18F-FDG PET/CT imaging.

Methods: Cytotoxicity of anti-EMMPRIN mAb alone or in combination with gemcitabine was measured for human pancreatic (MIA PaCa-2) cells by ATPLite assay. For in vivo animal study, six groups of SCID mice bearing orthotopic MIA PaCa-2 tumors was used at 21 days after cell implantation; groups 1 and 2 (n=5 per group) were i.v. injected with Tc-99m labeled anti-EMMPRIN mAb and isotype control mAb respectively. SPECT/CT imaging was conducted at 4 hours after injection, while biodistribution analysis was followed at 24 hours after injection. Groups 3-6 (n=6 per group) were i.p. injected with PBS (served as control), gemcitabine (120mg/kg BW), anti-EMMPRIN mAb (0.2mg), and combination, respectively, twice weekly for 2 weeks, while 18F-FDG PET/CT imaging was applied weekly for 3 weeks. Intratumoral SUVmean and tumor-volume changes during therapy were quantified. All tumors of groups 3-6 were collected at day 35, and Ki-67 and TUNEL staining were implemented.

Results: In vitro ATPLite assay demonstrated only modest killing efficacy by anti-EMMPRIN mAb alone or with gemcitabine. SPECT imaging showed the specific tumor uptake of Tc-99m-anti-EMMPRIN mAb. The %ID/g in liver, blood, and tumor of group 1 were 9.1±1.3, 13.4±3.0, and 27.6±3.2 respectively, while those of group 2 were 9.2±2.2, 10.8±1.3, and 5.8±1.7 respectively; tumor uptake of Tc-99m-anti-EMMPRIN mAb was significantly higher (p<0.001), while no differences were detected in liver and blood values. Intratumoral SUVmean changes of groups 3-6 relative to those at day 21 were 35±13, -19±19, 25±26, and -26±13% respectively at day 28, and 134±56, 60±32, 43±30, and -25±16% respectively at day 35; that of group 6 was significantly lower than those of the other groups (p<0.05), while no difference was detected among groups 3-5. Tumor-volume changes of groups 3-6 were 111±24, 72±26, 83±27, and 3±8% respectively at day 28, and 399±48, 275±57, 204±34, and 35±8% respectively at day 35; that of group 6 was significantly lower than those of groups 3-5 (p<0.05), and that of group 5 was also significantly lower than that of group 3 (p=0.042). The correlation between intratumoral SUVmean and tumor-volume changes was statistically significant (p=0.002). Proliferating cell density of group 6 was significantly lower than that of group 3 (p=0.008), while no difference was detected in apoptotic cell densities.

Conclusions: SUVmean of orthotopic pancreatic tumor xenografts was significantly decreased by the combination therapy, consistent with reduced proliferating cell density. These data provide support for clinical studies of anti-EMMPRIN therapy with gemcitabine for pancreatic cancer treatment, and the application of PET/CT with FDG to monitor efficacy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1795. doi:10.1158/1538-7445.AM2011-1795

  • ©2011 American Association for Cancer Research
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Cancer Research: 71 (8 Supplement)
April 2011
Volume 71, Issue 8 Supplement
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Abstract 1795: Therapy assessment of a novel anti-EMMPRIN antibody and gemcitabine in an orthotopic pancreatic-tumor murine model by FDG PET/CT imaging
Nemil Shah, Guihua Zhai, Joseph Knowles, Cecil Stockard, William Grizzle, Naomi Fineberg, Tong Zhou, Kurt Zinn, Eben Rosenthal and Hyunki Kim
Cancer Res April 15 2011 (71) (8 Supplement) 1795; DOI: 10.1158/1538-7445.AM2011-1795

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Abstract 1795: Therapy assessment of a novel anti-EMMPRIN antibody and gemcitabine in an orthotopic pancreatic-tumor murine model by FDG PET/CT imaging
Nemil Shah, Guihua Zhai, Joseph Knowles, Cecil Stockard, William Grizzle, Naomi Fineberg, Tong Zhou, Kurt Zinn, Eben Rosenthal and Hyunki Kim
Cancer Res April 15 2011 (71) (8 Supplement) 1795; DOI: 10.1158/1538-7445.AM2011-1795
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