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Molecular imaging of cancer biology ...
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Sprague, Jennifer Eryn.
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Molecular imaging of cancer biology using copper-64 radiolabeled peptides.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Molecular imaging of cancer biology using copper-64 radiolabeled peptides./
作者:
Sprague, Jennifer Eryn.
面頁冊數:
170 p.
附註:
Adviser: Carolyn J. Anderson.
Contained By:
Dissertation Abstracts International68-06B.
標題:
Health Sciences, Oncology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3268090
ISBN:
9780549070979
Molecular imaging of cancer biology using copper-64 radiolabeled peptides.
Sprague, Jennifer Eryn.
Molecular imaging of cancer biology using copper-64 radiolabeled peptides.
- 170 p.
Adviser: Carolyn J. Anderson.
Thesis (Ph.D.)--Washington University in St. Louis, 2007.
Copper-64 (t1/2 = 12.7 h) is a suitable radionuclide for both PET imaging as well as targeted radiotherapy due to its favorable decay characteristics (beta+ (17.3%), beta- (39%)). Peptides or antibodies targeting specific biological markers in vivo can be radiolabeled with 64CU through the use of a covalently bound bifunctional chelators (BFCs). This dissertation examines the ability to non-invasively detect markers associated with poor prognosis cancers. Initial studies utilized 64Cu-DOTA-CTT for detection of MMP-2 and MMP-9 expression by melanoma and breast cancer xenografts. However, this radiopharmaceutical showed limited imaging success due in large part to the poor in vivo stability properties of the 64Cu-DOTA chelate. This reinforced the need for more biologicaily stable BFCs of Cu(II). The cross-bridged chelator CB-TE2A had previously been identified as having improved in vivo stability, but it was not known if this macrocycle would retain these properties when conjugated to a peptide as a BFC. To test these properties, CB-TE2A was conjugated to a well-characterized peptide, Y3-TATE, in vitro affinity studies and in vivo biodistribution/microPET revealed little effect on peptide affinity and good in vivo clearance properties of 64Cu-CB-TE2A-Y3-TATE, consistent with good in vivo stability. Thus, CB-TE2A is a more stable BFC useful for PET imaging. Subsequently, CB-TE2A was conjugated to an RGD peptide for targeted imaging of the alphavbeta3 integrin using 64CU. Osteoclasts, bone degrading cells, play an important role in osteolytic bone metastases, and alphavbeta 3 is expressed at high levels by osteoclasts. Molecular imaging of osteoclasts in lytic bone lesions was carried out using 64Cu-CB-TE2A-RGD. Selective uptake of the RGD radiotracer by osteoclasts was demonstrated both in vitro and in vivo. The amount of bone surface area covered by osteoclasts correlated well with the uptake of 64Cu-CB-TE2A-RGD in bone. Imaging osteoclasts has the potential to facilitate earlier diagnosis or follow-up of treatment for osteolytic bone metastases.
ISBN: 9780549070979Subjects--Topical Terms:
1018566
Health Sciences, Oncology.
Molecular imaging of cancer biology using copper-64 radiolabeled peptides.
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