Micro-PET imaging of alphavbeta3-integrin expression with 18F-labeled dimeric RGD peptide.
The alphav integrins, which act as cell adhesion molecules, are closely involved with tumor invasion and angiogenesis. In particular, alphavbeta3 integrin, which is specifically expressed on proliferating endothelial cells and tumor cells, is a logical target for development of a radiotracer method to assess angiogenesis and anti-angiogenic therapy. In this study, a dimeric cyclic RGD peptide E[c(RGDyK)]2 was labeled with 18F (t(1/2) = 109.7 min) by using a prosthetic 4-[18F]fluorobenzoyl moiety to the amino group of the glutamate. The resulting [18F]FB-E[c(RGDyK)]2, with high specific activity (200-250 GBq/micromol at the end of synthesis), was administered to subcutaneous U87MG glioblastoma xenograft models for micro-PET and autoradiographic imaging as well as direct tissue sampling to assess tumor targeting efficacy and in vivo kinetics of this PET tracer. The dimeric RGD peptide demonstrated significantly higher tumor uptake and prolonged tumor retention in comparison with a monomeric RGD peptide analog [18F]FB-c(RGDyK). The dimeric RGD peptide had predominant renal excretion, whereas the monomeric analog was excreted primarily through the biliary route. Micro-PET imaging 1 hr after injection of the dimeric RGD peptide exhibited tumor to contralateral background ratio of 9.5 +/- 0.8. The synergistic effect of polyvalency and improved pharmacokinetics may be responsible for the superior imaging characteristics of [18F]FB-E[c(RGDyK)]2.
University of Southern California, Los Angeles, USA.
Xiaoyuan
X
Chen
Michel
M
Tohme
Ryan
R
Park
Yingping
Y
Hou
James R
JR
Bading
Peter S
PS
Conti
D000818:Animals; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000166:cytology; D002478:Cells, Cultured; D019281:Dimerization; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000473:pathology; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007553:Isotope Labeling; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012015:Reference Standards; D013997:Time Factors; D014183:Transplantation, Heterologous
D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D018698:Glutamic Acid; C047981:arginyl-glycyl-aspartic acid