Preclinical efficacy of the c-Met inhibitor CE-355621 in a U87 MG mouse xenograft model evaluated by 18F-FDG small-animal PET.

Molecular Imaging Program at Stanford, Bio-X Program, and Department of Radiology, Stanford University, Stanford, California 94305-5427, USA.
Journal of Nuclear Medicine (Impact Factor: 5.56). 02/2008; 49(1):129-34. DOI: 10.2967/jnumed.106.038836
Source: PubMed

ABSTRACT The purpose of this study was to evaluate the efficacy of CE-355621, a novel antibody against c-Met, in a subcutaneous U87 MG xenograft mouse model using (18)F-FDG small-animal PET.
CE-355621 or control vehicle was administered intraperitoneally into nude mice (drug-treated group, n = 12; control group, n = 14) with U87 MG subcutaneous tumor xenografts. Drug efficacy was evaluated over 2 wk using (18)F-FDG small-animal PET and compared with tumor volume growth curves.
The maximum %ID/g (percentage injected dose per gram of tissue) of (18)F-FDG accumulation in mice treated with CE-355621 remained essentially unchanged over 2 wk, whereas the %ID/g of the control tumors increased 66% compared with the baseline. Significant inhibition of (18)F-FDG accumulation was seen 3 d after drug treatment, which was earlier than the inhibition of tumor volume growth seen at 7 d after drug treatment.
CE-355621 is an efficacious novel antineoplastic chemotherapeutic agent that inhibits (18)F-FDG accumulation earlier than tumor volume changes in a mouse xenograft model. These results support the use of (18)F-FDG PET to assess early tumor response for CE-355621.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fluorescence imaging can track the expression of fluorescent protein and 18F-fluorodeoxyglucose based positron emission tomography ( [18F]FDG-PET) can evaluate the changes of [18F]FDG uptake in tumor cells during the antitumor treatment. In this work, fluorescence imaging and [18F]FDG-PET were both employed to monitor tumor response to Au nanorod-indocyanine green (AuNR-ICG) conjugates mediated therapy in a subcutaneous MDA-MB-231 mouse xenograft model. Serial fluorescence and [18F]FDG-PET images following the antitumor treatment were obtained and quantitative analysis revealed significant decreases in fluorescence intensity and metabolic activity in tumors treated with AuNR-ICG conjugates under near infrared laser irradiation. The results suggest that the combination of fluorescence and [18F]FDG-PET imaging can provide a noninvasive tool to assess the tumor response to antitumor therapy on a molecular scale.
    IEEE Transactions on Multimedia 08/2013; 15(5):1025-1030. DOI:10.1109/TMM.2013.2244204 · 1.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dual modality molecular imaging can capture concurrent molecular events and evaluate therapeutic efficacy from uniquely different perspectives based on different molecular targets. In this work, dual modality tomographic imaging, (18) F-fluorodeoxyglucose based positron emission tomography and subsurface fluorescence molecular tomography ([(18) F]FDG-PET/subsurface FMT), is proposed to monitor tumor response to cisplatin on a mouse xenograft model in vivo. One mouse was administered with cisplatin (1.0 mg/kg) by intraperitoneal injection once every day for 14 days, and another mouse was administered with saline to serve as the control. Dual modality [(18) F]FDG-PET/subsurface FMT imaging was conducted on days 0, 2, 5, 9, 15, and 22. In vivo imaging and quantitative analysis demonstrated the feasibility of [(18) F]FDG-PET/subsurface FMT imaging in tracking the changes of [(18) F]FDG tumor uptake and amount of red fluorescent protein (RFP) synthesized by tumor cells in the same mouse simultaneously. Dual modality [(18) F]FDG-PET/subsurface FMT imaging may thus provide a powerful tool for better understanding disease progress and treatment evaluation from different perspectives. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
    Journal of Biophotonics 11/2014; 7(11-12). DOI:10.1002/jbio.201300069 · 3.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Quantitative assessment of desmoplasia in pancreatic ductal adenocarcinoma (PDAC) may be critical for staging or prediction of response to therapy. We performed quantitative magnetization transfer (qMT) MRI measurements in 18 mouse xenograft tumors generated from three PDAC cell lines. The qMT parameter bound proton fraction (BPF) was found to be significantly higher in tumors grown using the BxPC-3 cell line (5.31 ± 0.87, mean ± standard deviation) compared with the BPF measured for tumors grown from Panc-1 (3.65 ± 0.60) and Capan-1 (1.50 ± 0.58) cell lines (P < 0.05 for each comparison). Histologic measurements demonstrated a similar trend; BxPC-3 tumors had significantly higher fibrosis levels (percentage of fibrotic tissue area, 6.21 ± 2.10) compared with Panc-1 (2.88 ± 1.13) and Capan-1 (1.69 ± 1.01) tumors. BPF was well correlated with quantitative fibrosis levels (r = 0.77, P < 0.01). Our results indicate that qMT measurements offer the potential to noninvasively quantify fibrosis levels in PDAC mouse xenograft models and thus serve as a valuable in vivo biomarker of desmoplasia in PDAC. Copyright © 2013 John Wiley & Sons, Ltd.
    NMR in Biomedicine 08/2013; DOI:10.1002/nbm.3004 · 3.56 Impact Factor

Full-text (2 Sources)

Available from
May 28, 2014