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Targeted molecular imaging of brain ...

Hernandez, Reinier.

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Targeted molecular imaging of brain cancer.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Targeted molecular imaging of brain cancer./
Author:	Hernandez, Reinier.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	136 p.
Notes:	Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
Contained By:	Dissertation Abstracts International77-12B(E).
Subject:	Medical imaging. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10146694
ISBN:	9781369020052

Targeted molecular imaging of brain cancer.
Hernandez, Reinier.

Targeted molecular imaging of brain cancer. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 136 p.

Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016.

Brain cancer remains amongst the most lethal diseases. The urgent necessity for more effective clinical management paradigms has galvanized the emergence of novel, patient-tailored, diagnostic and therapeutic strategies based on targeting tumor-specific antigens. This dissertation focused on imaging the expression of several tumor-associated targets implicated in the proliferation, angiogenesis, tumor invasion, metastasis, and cancer stem cells traits of aggressive brain cancers using positron emission tomography (PET), and to a lesser extent fluorescence imaging.

ISBN: 9781369020052Subjects--Topical Terms:

3172799
Medical imaging.

Targeted molecular imaging of brain cancer.
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245 1 0 $a Targeted molecular imaging of brain cancer.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 136 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
500 $a Adviser: Weibo Cai.
502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2016.
520 $a Brain cancer remains amongst the most lethal diseases. The urgent necessity for more effective clinical management paradigms has galvanized the emergence of novel, patient-tailored, diagnostic and therapeutic strategies based on targeting tumor-specific antigens. This dissertation focused on imaging the expression of several tumor-associated targets implicated in the proliferation, angiogenesis, tumor invasion, metastasis, and cancer stem cells traits of aggressive brain cancers using positron emission tomography (PET), and to a lesser extent fluorescence imaging.
520 $a Chapters 2 and 3 describe the design and generation of novel RGD peptide-based radiotracers for in vivo PET imaging of integrin alpha vbeta3 expression. These tracers were engineered to feature enhanced radionuclidic, targeting, and pharmacokinetic properties that allowed elevated accumulation of the tracer in subcutaneous glioblastomas and rapid clearance from circulation and non-target tissues. In addition, several studies confirmed the specificity of the radiotracer towards integrin alpha vbeta3. We also concluded that the positron emitting radiometal 44Sc possesses properties (e.g., half-live, beta+ branching ratio, coordination chemistry) well-suited for peptide-based imaging.
520 $a CD146 expression has been linked to increased cancer aggressiveness, metastasis, and decreased patient survival in a plethora of cancer, including brain cancer. In Chapters 4 and 5, we set out to produce YY146, an anti-CD146 monoclonal antibody, for noninvasive PET imaging of glioblastoma. The radiotracers 64Cu-NOTA-YY146 and 89Zr-Df-YY146 showed preferential uptake in the tumors of mice bearing subcutaneous or orthotopic U87MG xenografts, allowing for an accurate delineation of small brain nodules in the PET images. Tumor uptake correlated with CD146 expression levels in a highly specific manner. More importantly, histological analysis of human brain cancer tissue uncovered the clinical relevance of CD146 as a target of glioblastoma.
520 $a In chapter 6, given the coexpression of EGFR and CD105 in glioblastomas, we generated a bispecific immunoconjugate to target EGFR and CD105 simultaneously. Based on in vivo PET imaging, the bispecific construct, which features two antibody Fab fragments conjugated using "click" chemistry, revealed significantly higher uptake in U87MG tumors, compared to each monovalent Fab fragment. This synergistic enhancement in tumor affinity allowed for impressive tumor-to-background ratios that facilitated detection of malignancies at an early stage while maintaining excellent specificity.
590 $a School code: 0262.
650 4 $a Medical imaging. $3 3172799
650 4 $a Oncology. $3 751006
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710 2 $a The University of Wisconsin - Madison. $b Medical Physics. $3 2097834
773 0 $t Dissertation Abstracts International $g 77-12B(E).
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