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01-04-2012 | Research Article

¹⁸F-FDG PET/CT Imaging Detects Therapy Efficacy of Anti-EMMPRIN Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts

Authors: Nemil Shah, Guihua Zhai, Joseph A. Knowles, Cecil R. Stockard, William E. Grizzle, Naomi Fineberg, Tong Zhou, Kurt R. Zinn, Eben L. Rosenthal, Hyunki Kim

Published in: Molecular Imaging and Biology | Issue 2/2012

Abstract

Purpose

The objective of this study is to evaluate the therapeutic response to a novel monoclonal antibody targeting human extracellular matrix metalloproteinase inducer (EMMPRIN) in combination with gemcitabine in a pancreatic-tumor xenograft murine model by sequential 2-deoxy-2-[18F]fluoro-d-glucose (¹⁸F-FDG) positron emission tomography/computed tomgraphy (PET/CT) imaging.

Procedures

Four groups of SCID mice bearing orthotopic pancreatic tumor xenografts were injected with phosphate-buffered saline, gemcitabine (120 mg/kg BW), anti-EMMPRIN antibody (0.2 mg), or combination, respectively, twice weekly for 2 weeks, while ¹⁸F-FDG PET/CT imaging was performed weekly for 3 weeks. Changes in mean standardized uptake value (SUV_mean) of ¹⁸F-FDG and volume of tumors were determined.

Results

The tumor SUV_mean change in the group receiving combination therapy was significantly lower than those of the other groups. Tumor-volume changes of groups treated with anti-EMMPRIN monotherapy or combined therapy were significantly lower than that of the control group.

Conclusions

These data provide support for clinical studies of anti-EMMPRIN therapy with gemcitabine for pancreatic cancer treatment.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249PubMedCrossRef

Klapman J, Malafa MP (2008) Early detection of pancreatic cancer: why, who, and how to screen. Cancer Control 15:280–287PubMed

Burris HA, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413PubMed

Cardenes HR, Chiorean EG, Dewitt J, Schmidt M, Loehrer P (2006) Locally advanced pancreatic cancer: current therapeutic approach. Oncologist 11:612–623PubMedCrossRef

Stathis A, Moore MJ (2010) Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7:163–172PubMedCrossRef

Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB (2002) Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 20:3270–3275PubMedCrossRef

Heinemann V, Quietzsch D, Gieseler F et al (2006) Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 24:3946–3952PubMedCrossRef

Rocha Lima CM, Green MR, Rotche R et al (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 22:3776–3783PubMedCrossRef

Louvet C, Labianca R, Hammel P et al (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23:3509–3516PubMedCrossRef

10.

Abou-Alfa GK, Letourneau R, Harker G et al (2006) Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol 24:4441–4447PubMedCrossRef

11.

Moore MJ, Goldstein D, Hamm J et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25:1960–1966PubMedCrossRef

12.

Kindler HL (2007) Pancreatic cancer: an update. Curr Oncol Rep 9:170–176PubMedCrossRef

13.

Kindler HL (2005) Front-line therapy of advanced pancreatic cancer. Semin Oncol 32:S33–S36PubMedCrossRef

14.

Biswas C, Zhang Y, DeCastro R et al (1995) The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res 55:434–439PubMed

15.

Suzuki S, Sato M, Senoo H, Ishikawa K (2004) Direct cell-cell interaction enhances pro-MMP-2 production and activation in co-culture of laryngeal cancer cells and fibroblasts: involvement of EMMPRIN and MT1-MMP. Exp Cell Res 293:259–266PubMedCrossRef

16.

Ellenrieder V, Alber B, Lacher U et al (2000) Role of MT-MMPs and MMP-2 in pancreatic cancer progression. Int J Cancer 85:14–20PubMedCrossRef

17.

Tang Y, Nakada MT, Kesavan P et al (2005) Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res 65:3193–3199PubMed

18.

Bougatef F, Quemener C, Kellouche S et al (2009) EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2alpha-mediated regulation of soluble VEGF isoforms and their receptor VEGFR-2. Blood 114:5547–5556PubMedCrossRef

19.

Zheng HC, Takahashi H, Murai Y et al (2006) Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. Br J Cancer 95:1371–1378PubMedCrossRef

20.

Riethdorf S, Reimers N, Assmann V et al (2006) High incidence of EMMPRIN expression in human tumors. Int J Cancer 119:1800–1810PubMedCrossRef

21.

Dandekar M, Tseng JR, Gambhir SS (2007) Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts. J Nucl Med 48:602–607PubMedCrossRef

22.

Kroep JR, Van Groeningen CJ, Cuesta MA et al (2003) Positron emission tomography using 2-deoxy-2-[18F]-fluoro-D-glucose for response monitoring in locally advanced gastroesophageal cancer; a comparison of different analytical methods. Mol Imaging Biol 5:337–346PubMedCrossRef

23.

Kelloff GJ, Hoffman JM, Johnson B et al (2005) Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 11:2785–2808PubMedCrossRef

24.

Barber TW, Kalff V, Cherk MH, Yap KS, Evans P, Kelly MJ (2010) (18)F-FDG PET/CT influences management in patients with known or suspected pancreatic cancer. Intern Med J. doi:10.1111/j.1445-5994.2010.02257.x

25.

Mataki Y, Shinchi H, Kurahara H et al (2009) Clinical usefulness of FDG-PET for pancreatic cancer. Gan To Kagaku Ryoho 36:2516–2520PubMed

26.

Maisey NR, Webb A, Flux GD et al (2000) FDG-PET in the prediction of survival of patients with cancer of the pancreas: a pilot study. Br J Cancer 83:287–293PubMedCrossRef

27.

Higashi T, Sakahara H, Torizuka T et al (1999) Evaluation of intraoperative radiation therapy for unresectable pancreatic cancer with FDG PET. J Nucl Med 40:1424–1433PubMed

28.

Kuwatani M, Kawakami H, Eto K et al (2009) Modalities for evaluating chemotherapeutic efficacy and survival time in patients with advanced pancreatic cancer: comparison between FDG-PET, CT, and serum tumor markers. Intern Med 48:867–875PubMedCrossRef

29.

Schellenberg D, Quon A, Minn AY et al (2010) 18Fluorodeoxyglucose PET is prognostic of progression-free and overall survival in locally advanced pancreas cancer treated with stereotactic radiotherapy. Int J Radiat Oncol Biol Phys 77:1420–1425PubMedCrossRef

30.

Schneiderhan W, Diaz F, Fundel M et al (2007) Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay. J Cell Sci 120:512–519PubMedCrossRef

31.

Larsen SK, Solomon HF, Caldwell G, Abrams MJ (1995) [99mTc]tricine: a useful precursor complex for the radiolabeling of hydrazinonicotinate protein conjugates. Bioconjug Chem 6:635–638PubMedCrossRef

32.

Lowry O, Rosebrough N, Farr L, Randall R (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMed

33.

Prasad R, Ratib O, Zaidi H (2010) Performance evaluation of the FLEX triumph X-PET scanner using the national electrical manufacturers association NU-4 standards. J Nucl Med 51:1608–1615PubMedCrossRef

34.

Kim H, Morgan DE, Buchsbaum DJ et al (2008) Early therapy evaluation of combined anti-death receptor 5 antibody and gemcitabine in orthotopic pancreatic tumor xenografts by diffusion-weighted magnetic resonance imaging. Cancer Res 68:8369–8376PubMedCrossRef

35.

Neter J, Kutner MH, Nachtsheim JC, Wasserman W (1996) Applied linear statistical models. McGraw-Hill, Columbus

36.

Hertzog C, Rovine M (1985) Repeated-measures analysis of variance in developmental research: selected issues. Child Dev 56:787–809PubMedCrossRef

37.

Rodgers JL, Nicewander WA (1988) Thirteen ways to look at the correlation coefficient. Am Stat 42:59–66CrossRef

38.

Escorcia FE, Henke E, McDevitt MR et al (2010) Selective killing of tumor neovasculature paradoxically improves chemotherapy delivery to tumors. Cancer Res 70:9277–9286PubMedCrossRef

39.

Dean NR, Newman JR, Helman EE et al (2009) Anti-EMMPRIN monoclonal antibody as a novel agent for therapy of head and neck cancer. Clin Cancer Res 15:4058–4065PubMedCrossRef

Title: 18F-FDG PET/CT Imaging Detects Therapy Efficacy of Anti-EMMPRIN Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts
Authors: Nemil Shah
Guihua Zhai
Joseph A. Knowles
Cecil R. Stockard
William E. Grizzle
Naomi Fineberg
Tong Zhou
Kurt R. Zinn
Eben L. Rosenthal
Hyunki Kim
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: Molecular Imaging and Biology / Issue 2/2012
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-011-0491-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

¹⁸F-FDG PET/CT Imaging Detects Therapy Efficacy of Anti-EMMPRIN Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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