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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: March 11, 2008.

Chemical name:N-4-[18F]Fluorobenzoyl-c(RGDyK)image 10318726 in the ncbi pubchem database
Abbreviated name:[18F]FB-c(RGDyK), [18F]FB-RGD
Agent Category:Peptide
Target:Integrin αvβ3
Target Category:Receptor binding
Method of detection:PET
Source of signal:18F
  • Checkbox In vitro
  • Checkbox Rodents
Click on the above structure for additional information in PubChem.



Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell-cell and cell-matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. αvβ3 integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of αvβ3 integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. αvβ3 antagonists are being studied as antitumor and antiangiogenic agents and the agonists as angiogenic agents for coronary angiogenesis (6, 8, 9). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including αvβ3. Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10).

Most of the cyclic RGD peptides are monomeric and composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to αvβ3 (IC50, 7-40 nM) but not to αvβ5 (IC50, 600-4,000 nM) or αIIbβ3 (IC50, 700-5,000 nM) integrin. [18F]FB-c(RGDyK) was synthesized to study in vivo biodistribution of the tracer in tumor-bearing mice. [18F]FB-c(RGDyK) was found to have high accumulation in tumors, but it also had a high tumor washout and biliary excretion into the gallbladder and intestines (12). A dimeric analog was also synthesized as [18F]FB-E[c(RGDyK)]2, which was shown to have higher tumor uptake than the monomer and predominantly renal excretion (13).



N-Succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) was synthesized in two steps from [18F]KF (Kryptofix 2.2.2./K2CO3) in 65 min (12). The decay-corrected yields of [18F]SFB were 60-65%, based on starting [18F]KF. [18F]SFB was used to conjugate c(RGDyK) and E[c(RGDyK)]2 to form [18F]FB-c(RGDyK) and [18F]FB-E[c(RGDyK)]2, respectively. Radiochemical purities >99% were obtained for both peptides, and radiochemical yields were 35-45% for the monomer and 20-30% for the dimers (12). The specific activity was 222 GBq/μmol (6 Ci/μmol) at end of synthesis. Total synthesis time was about 200 min including the final high-performance liquid chromatography purification.

In Vitro Studies: Testing in Cells and Tissues


A receptor-binding assay (13) with 125I-c(RGDyK) was established using a primary human brain capillary endothelial cells, which contain αvβ3 and αvβ5 integrin. FB-c(RGDyK), FB-E[c(RGDyK)]2, c(RGDyK), and [c(RGDyK)]2 had IC50 values of 16.9 ± 0.5, 6.7 ± 0.5, 3.5 ± 0.3, and 2.3 ± 0.7 nM, respectively (13). Haubner et al. (11) showed that c(RGDyK(SAA)) had IC50 values of 20, 4,000, and 3,000 nM for αvβ3, αvβ5, and αIIbβ3, respectively.

Animal Studies



Chen et al. (12) performed biodistribution studies of [18F]FB-c(RGDyK) in nude mice, using a U87MG glioblastoma s.c. xenograft model. Data were obtained at 30, 60, and 120 min after injection. [18F]FB-c(RGDyK) had very rapid blood clearance, resulting in very low activity in the blood, bone, and muscle at 30, 60, and 120 min (<0.5% of injected dose (ID)/g). There was little defluorination of the tracer in the bone. The initial tracer accumulation in the αvβ3-integrin-expressing U87MG tumor was about 3% ID/g at 30 min and decreased to about 1.5% ID/g at 2 h. Tumor uptake of radioactivity was blocked by co-injection of unlabeled c(RGDyK) from 2.6% ID/g to 0.35% ID/g (5 mg/kg) and 0.26% ID/g (15 mg/kg). The tracer had very fast renal clearance. At 60 min, the highest and second highest radioactive concentrations were found in the urine and gallbladder, followed by the tumor, kidney, and liver. Tumor/blood and tumor/muscle ratios at 2 h were high (21 and 8.2, respectively). [18F]FB-RGD demonstrated rapid blood clearance and fast tumor accumulation. [18F]FB-E[c(RGDyK)]2 showed a similar biodistribution profile in this tumor model except that tumor accumulation was significantly higher than for the monomer (13).

[18F]FB-c(RGDyK) positron emission tomography imaging studies in mice with an orthotopic U251T human brain tumor showed the tumor in the brain with low background in normal brain. c(RGDyK) pretreatment lowered the tumor/brain ratio from 8 to 2.5 (12).

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

P20 CA86532, R01 CA82989


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