Abstract | PURPOSE: PROCEDURES: Dimeric RGD peptides E[c(RGDyK)]2 and E[c(RGDfK)]2 were conjugated with 1,4,7,10-tetraazadodecane-N,N',N",N"'-tetraacetic acid ( DOTA) and labeled with positron emitter 64Cu(t(1/2)=12.8 h, beta+=19%). Both 64Cu- DOTA-E[c(RGDyK)]2 and 64Cu- DOTA-E[c(RGDfK)]2 were used in biodistribution, microPET imaging and whole-body autoradiography studies in athymic female nude mice with orthotopically growing MDA-MB-435 breast carcinoma xenografts. RESULTS: At all time points, activity accumulation of 64)Cu- DOTA-E[c(RGDyK)]2 in tumors was significantly higher compared to the D-Phe analog. Liver uptake of the D-Tyr derivative was lower than the D-Phe derivative at early time points but the difference became marginal with time. Overall, 64Cu- DOTA-E[c(RGDyK)]2 yielded better position emission tomography (PET) images in orthotopic MDA-MB-435 bearing mice than did 64Cu- DOTA-E[c(RGDfK)]2. Both radiotracers had alphav-integrin specific tumor activity accumulation, as demonstrated by significant reduction of uptake with a coinjected blocking dose of c(RGDyK). CONCLUSIONS: The radiolabeled dimeric RGD peptides 64Cu- DOTA-E[c(RGDyK)]2 and 64Cu- DOTA-E[c(RGDfK)]2 have high and specific tumor uptake in a human breast cancer tumor xenograft, with the D-Tyr derivative showing better in vivo kinetics than the D-Phe derivative, most likely due to the increased hydrophilicity of the D-Tyr. Both dimeric peptides showed better tumor retention than the previously tested monomeric RGD counterparts, presumably because of bivalency and increase in apparent molecular size.
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Authors | Xiaoyuan Chen, Shuang Liu, Yingping Hou, Michel Tohme, Ryan Park, James R Bading, Peter S Conti |
Journal | Molecular imaging and biology
(Mol Imaging Biol)
2004 Sep-Oct
Vol. 6
Issue 5
Pg. 350-9
ISSN: 1536-1632 [Print] United States |
PMID | 15380745
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Copper Radioisotopes
- Integrin alphaV
- Oligopeptides
- arginyl-glycyl-aspartic acid
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Topics |
- Animals
- Autoradiography
- Breast Neoplasms
(diagnostic imaging)
- Copper Radioisotopes
- Dimerization
- Female
- Humans
- Integrin alphaV
(genetics, metabolism)
- Kinetics
- Mice
- Mice, Nude
- Oligopeptides
(chemical synthesis, metabolism)
- Positron-Emission Tomography
- Radiography
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