Linked Life Data

14733582

Source:http://linkedlifedata.com/resource/pubmed/id/14733582

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-21
pubmed:abstractText
Cell adhesion molecules alphavbeta3 and alphavbeta5 play a pivotal role in tumor angiogenesis and metastasis. Antiangiogenic therapy by using small peptide antagonists of alphav-integrins slows tumor growth and prevents tumor spread. The ability to visualize and quantify integrin expression will enable selection of appropriate patients for clinical trials, following determination of treatment efficacy and development of new potent drugs. We have previously labeled cyclic RGD peptide c(RGDyK) with 125I and 18F and applied the radiotracers to both subcutaneous and orthotopic brain tumor models. Here we conjugated c(RGDyK) with 1,4,7,10-tetraaza-1,4,7,10-tetradodecane-N,N',N' ',N' "-tetraacetic acid (DOTA) and labeled the DOTA-RGD conjugate with 64Cu (t1/2) = 12.8 h, 19% beta+) in high radiochemical purity and specific activity. The tumor targeting ability and in vivo kinetics of 64Cu-DOTA-RGD was compared with [18F]FB-RGD and 125I-RGD in orthotopic MDA-MB-435 breast cancer model. All three radiotracers revealed fast blood clearance and high tumor-to-blood and tumor-to-muscle ratios. 125I-RGD had higher tumor uptake than the corresponding 18F and 64Cu analogues. [18F]FB-RGD indicated a fast tumor washout rate and an unfavorable hepatobiliary excretion pathway, resulting in significant activity accumulation in gallbladder and intestines. 64Cu-DOTA-RGD had prolonged tumor retention (1.44 +/- 0.09 %ID/g at 4 h postinjection) and persistent uptake in the liver. All three tracers revealed receptor specific tumor accumulation which were illustrated by effective blocking via coinjection with a blocking dose of c(RGDyK). Static microPET imaging and whole-body autoradiography showed strong contrast from the contralateral background. In conclusion, overall molecular charge and characteristics of radiolabels have profound effects on tumor accumulation and in vivo kinetics of radiolabeled RGD peptide. Further modification of the RGD peptide and optimization of the tracer for prolonged tumor uptake and improved in vivo kinetics are being explored.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1043-1802
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14733582-Animals, pubmed-meshheading:14733582-Autoradiography, pubmed-meshheading:14733582-Breast Neoplasms, pubmed-meshheading:14733582-Chromatography, High Pressure Liquid, pubmed-meshheading:14733582-Copper Radioisotopes, pubmed-meshheading:14733582-Female, pubmed-meshheading:14733582-Fluorine Radioisotopes, pubmed-meshheading:14733582-Humans, pubmed-meshheading:14733582-Indicators and Reagents, pubmed-meshheading:14733582-Integrin alphaV, pubmed-meshheading:14733582-Isotope Labeling, pubmed-meshheading:14733582-Mice, pubmed-meshheading:14733582-Neoplasm Transplantation, pubmed-meshheading:14733582-Oligopeptides, pubmed-meshheading:14733582-Radiopharmaceuticals, pubmed-meshheading:14733582-Tissue Distribution, pubmed-meshheading:14733582-Tomography, Emission-Computed, pubmed-meshheading:14733582-Transplantation, Heterologous
pubmed:articleTitle
MicroPET and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD peptide.
pubmed:affiliation
PET Imaging Science Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't