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Novel target for peptide-based imaging and treatment of brain tumors.

ABSTRACT: Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared with the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3) as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histologic grade of the tumor, suggesting MDGI as a novel marker for malignant gliomas.

SUBMITTER: Hyvonen M

PROVIDER: S-EPMC4007056 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Novel target for peptide-based imaging and treatment of brain tumors.

Hyvönen Maija M Enbäck Juulia J Huhtala Tuulia T Lammi Johanna J Sihto Harri H Weisell Janne J Joensuu Heikki H Rosenthal-Aizman Katri K El-Andaloussi Samir S Langel Ulo U Närvänen Ale A Bergers Gabriele G Laakkonen Pirjo P

Molecular cancer therapeutics 20140203 4

Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging ...[more]

PMID: 24493698

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Project description:MRI offers a tremendous armamentarium of different methods that can be employed in brain tumor characterization. MR diffusion imaging has become a widely accepted method to probe for the presence of fluid pools and molecular tissue water mobility. For most clinical applications of diffusion imaging, it is assumed that the diffusion signal vs diffusion weighting factor b decays monoexponentially. Within this framework, the measurement of a single diffusion coefficient in brain tumors permits an approximate categorization of tumor type and, for some tumors, definitive diagnosis. In most brain tumors, when compared with normal brain tissue, the diffusion coefficient is elevated. The presence of peritumoral edema, which also exhibits an elevated diffusion coefficient, often precludes the delineation of the tumor on the basis of diffusion information alone. Serially obtained diffusion data are useful to document and even predict the cellular response to drug or radiation therapy. Diffusion measurements in tissues over an extended range of b factors have clearly shown that the monoparametric description of the MR diffusion signal decay is incomplete. Very high diffusion weighting on clinical systems requires substantial compromise in spatial resolution. However, after suitable analysis, superior separation of malignant brain tumors, peritumoral edema and normal brain tissue can be achieved. These findings are also discussed in the light of tissue-specific differences in membrane structure and the restrictions exerted by membranes on diffusion. Finally, measurement of the directional dependence of diffusion permits the assessment of white matter integrity and dislocation. Such information, particularly in conjunction with advanced post-processing, is considered to be immensely useful for therapy planning. Diffusion imaging, which permits monoexponential analysis and provides directional diffusion information, is performed routinely in brain tumor patients. More advanced methods require improvement in acquisition speed and spatial resolution to gain clinical acceptance.

Dataset Information

Novel target for peptide-based imaging and treatment of brain tumors.

Publications

Novel target for peptide-based imaging and treatment of brain tumors.

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