Abstract 1795: Therapy assessment of a novel anti-EMMPRIN antibody and gemcitabine in an orthotopic pancreatic-tumor murine model by FDG PET/CT imaging
Authors: Nemil Shah, Guihua Zhai, Joseph Knowles, Cecil Stockard, William Grizzle, Naomi Fineberg, Tong Zhou, Kurt Zinn, Eben Rosenthal, Hyunki Kim
Journal: Cancer Research (2011)

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&amp;lt;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&amp;lt;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&amp;lt;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