18F-FDG PET/CT Imaging Detects Therapy Efficacy of Anti-EMMPRIN Antibody and Gemcitabine in Orthotopic Pancreatic Tumor Xenografts
- 244 Downloads
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.
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 (SUVmean) of 18F-FDG and volume of tumors were determined.
The tumor SUVmean 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.
These data provide support for clinical studies of anti-EMMPRIN therapy with gemcitabine for pancreatic cancer treatment.
Key wordsFDG-PET CT EMMPRIN Gemcitabine Pancreatic cancer
Financial support was provided by an HSF-GEF Scholar Award, AACR-PANCAN Career Development Award, National Cancer Institute (R01CA142637 and 5K08CA102154), the Pancreatic SPORE (CA101955), and the UAB small animal imaging shared facility (5P30CA013148). Authors thank Sharon Samuel, Lee Whitworth, and Amber Martin for assistance with growing cells, in vitro assays, animal monitoring, and imaging. All experiments complied will current regulatory and ethical requirements.
Conflict of interest
No authors have conflict of interest to report.
- 6.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 20:3270–3275PubMedCrossRefGoogle Scholar
- 8.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 22:3776–3783PubMedCrossRefGoogle Scholar
- 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
- 35.Neter J, Kutner MH, Nachtsheim JC, Wasserman W (1996) Applied linear statistical models. McGraw-Hill, ColumbusGoogle Scholar