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  • American Association for Cancer Research (AACR)  (3)
  • 1
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 22 ( 2016-11-15), p. 6463-6470
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 22 ( 2016-11-15), p. 6463-6470
    Abstract: The vast majority of cancers exhibit increased glucose uptake and glycolysis regardless of oxygen availability. This metabolic shift leads to an enhanced production of lactic acid that decreases extracellular pH (pHe), a hallmark of the tumor microenvironment. In this way, dysregulated tumor pHe and upregulated glucose metabolism are linked tightly and their relative assessment may be useful to gain understanding of the underlying biology. Here we investigated noninvasively the in vivo correlation between tumor 18F-FDG uptake and extracellular pH values in a murine model of HER2+ breast cancer. Tumor extracellular pH and perfusion were assessed by acquiring MRI-CEST (chemical exchange saturation transfer) images on a 3T scanner after intravenous administration of a pH-responsive contrast agent (iopamidol). Static PET images were recorded immediately after MRI acquisitions to quantify the extent of 18F-FDG uptake. We demonstrated the occurrence of tumor pHe changes that report on acidification of the interstitial fluid caused by an accelerated glycolysis. Combined PET and MRI-CEST images reported complementary spatial information of the altered glucose metabolism. Notably, a significant inverse correlation was found between extracellular tumor pH and 18F-FDG uptake, as a high 18F-FDG uptake corresponds to lower extracellular pH values. These results show how merging the information from 18F-FDG-uptake and extracellular pH measurements can improve characterization of the tumor microenvironment. Cancer Res; 76(22); 6463–70. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 6 ( 2010-03-15), p. 2180-2190
    Abstract: Specific targeting of tumors by combined delivery of drugs and of imaging agents represents an attractive strategy for treatment of cancer. The aim of the present study was to investigate whether neural cell adhesion molecule (NCAM)–targeted liposomes may enhance drug delivery and allow magnetic resonance imaging (MRI) in a severe combined immunodeficient mouse model of NCAM-positive Kaposi's sarcoma. NCAM-binding peptide–coated liposomes loaded with both doxorubicin and a lipophilic gadolinium (Gd) derivative were generated. NCAM-targeted liposomes induced an enhanced in vitro doxorubicin internalization within Kaposi's cells as detected by MRI with respect to untargeted polyethylene glycol liposomes. Internalization resulted in enhanced apoptosis. In vivo weekly administration of NCAM-targeted liposomes containing 5 mg/kg doxorubicin for 4 consecutive weeks induced a significant reduction of tumor mass and vascularization and enhanced cell necrosis and apoptosis with respect to untargeted liposomes. These effects were associated with an enhanced concentration of doxorubicin within the tumor and a reduced systemic toxicity of doxorubicin. By electron microscopy, NCAM-targeted liposomes were detected mainly within tumor cells whereas the untargeted liposomes were mainly accumulated in the extracellular space. Gd-labeled liposomes allowed the MRI visualization of drug delivery in the tumor region. The intensity of MRI signal was partially hampered by the “quenching” of the attainable relaxation enhancement on endosomal entrapment of the Gd-labeled liposomes. In conclusion, targeting NCAM may be a suitable strategy for specific drug delivery and imaging by liposomes in NCAM-expressing tumors. Moreover, treatment with NCAM-targeted liposomes showed enhanced therapeutic effect and reduced toxicity with respect to untargeted liposomes. Cancer Res; 70(6); 2180–90
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 18 ( 2006-09-15), p. 9196-9201
    Abstract: Tumor vessel imaging could be useful in identifying angiogenic blood vessels as well as being a potential predictive marker of antiangiogenic treatment response. We recently reported the expression of the neural cell adhesion molecule (NCAM) in the immature and tumor endothelial cell (TEC) lining vessels of human carcinomas. Exploiting an in vivo model of human tumor angiogenesis obtained by implantation of TEC in Matrigel in severe combined immunodeficiency mice, we aimed to image angiogenesis by detecting the expression of NCAM with magnetic resonance imaging. The imaging procedure consisted of (a) targeting NCAMs with a biotinylated derivative of C3d peptide that is known to have high affinity for these epitopes and (b) delivery of a streptavidin/gadolinium (Gd)-loaded apoferritin 1:1 adduct at the biotinylated target sites. The remarkable relaxation enhancement ability of the Gd-loaded apoferritin system allowed the visualization of TEC both in vitro and in vivo when organized in microvessels connected to the mouse vasculature. Gd-loaded apoferritin displayed good in vivo stability and tolerability. The procedure reported herein may be easily extended to the magnetic resonance visualization of other epitopes suitably targeted by proper biotinylated vectors. (Cancer Res 2006; 66(18): 9196-201)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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