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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 Center for Biotechnology Information, NLM, NIH

Created: ; Last Update: July 1, 2009.

Chemical name:[18F]Fluorobenzyl-PEG3-Glu-c(RGDyK)-bombesin[7-14]
Abbreviated name:[18F]FB-PEG3-Glu-RGD-BBN
Agent category:Peptide
Target:Gastrin-releasing peptide receptor (GRPR), integrin αvβ3
Target category:Receptor
Method of detection:Positron emission tomography (PET)
Source of signal\contrast:18F
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about integrin αvβ3.



The amphibian bombesin (BBN or BN, a peptide of 14 amino acids) is an analog of human gastrin-releasing peptide (GRP, a peptide of 27 amino acids), which binds to GRP receptors (GRPR) with high affinity and specificity (1, 2). Both GRP and BBN share an amidated C-terminus sequence homology of seven amino acids, Trp-Ala-Val-Gly-His-Leu-Met-NH2. BBN-Like peptides have been shown to induce various biological responses in diverse tissues, including the central nervous system and the gastrointestinal system. They also act as potential growth factors for both normal and neoplastic tissues (3). Specific BBN receptors (BBN-R) have been identified on central nervous system and gastrointestinal tissues and on a number of tumor cell lines (4). The BBN-R superfamily includes at least four different subtypes, namely the GRPR subtype (BB2), the neuromedin B (NMB) receptor subtype (BB1), the BB3 subtype, and the BB4 subtype. The findings of GRPR overexpression in various human tumors, such as breast, prostate, lung, colon, ovarian, and pancreatic cancers, provide opportunities for tumor imaging by designing specific molecular imaging agents to target the GRPR (5, 6).

Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (7). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The αvβ3 integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (8-13). Expression of the αvβ3 integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. Antagonists of αvβ3 are being studied as antitumor and antiangiogenic agents, and agonists of αvβ3 are being studied as angiogenic agents for coronary angiogenesis (12, 14, 15). A peptide 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 ligands have been introduced for imaging of tumors and tumor angiogenesis (16).

Because prostate cancer expresses both GRPR and αvβ3, Liu et al. (17) designed an RGD-BBN heterodimer in which BBN[7-14] and c(RGDyK) were connected with a glutamate linker (BBN on the Glu side-chain γ-carboxylate group and on the Glu side-chain α-carboxylate group). A spacer, 11-amino-3,6,9-trioxaundecanoic acid (PEG3), was placed on the glutamate α-amino group of Glu-RGD-BBN to increase the hydrophilicity and to relieve the steric hindrance. N-Succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) was used to synthesize [18F]FB-PEG3-Glu-RGD-BBN for tumor imaging in vivo.



Glu-RGD-BBN was prepared with solid-phase peptide synthesis with subsequent addition of a PEG3 group to form PEG3-Glu-RGD-BBN (17). [18F]SFB was added to a solution of PEG3-Glu-RGD-BBN. The mixture was heated for 30 min at 60°C. The product, [18F]FB-PEG3-Glu-RGD-BBN, was purified with high-performance liquid chromatography with a yield of 42% based on [18F]SFB and a radiochemical purity of >99%. The specific activity of [18F]FB-PEG3-Glu-RGD-BBN was estimated to be ~100 GBq/µmol (2.7 Ci/µmol) at the end of synthesis. [18F]FB is conjugated to the amino group of PEG3.

In Vitro Studies: Testing in Cells and Tissues


Liu et al. (17) performed in vitro inhibition studies of RGD, PEG3-Glu-RGD-BBN, and FB-PEG3-Glu-RGD-BBN in cultured U87MG cells with 125I-echistatin. The 50% inhibition concentration (IC50) values were 11.2, 10.8, and 13.8 nM, respectively. In vitro inhibition studies of Aca-BBN, PEG3-Glu-RGD-BBN, and FB-PEG3-Glu-RGD-BBN were also performed in cultured PC-3 cells with 125I-BBN. The IC50 values were 79.0, 85.5, and 73.3 nM, respectively. Therefore, the FB-PEG3-RGD-BBN heterodimer exhibited comparable binding affinities for αvβ3 integrin with GRPR and αvβ3 integrin receptor as the parent RGD and BNN peptides. PC-3 cells express a high level of GRPR and a moderate level of αvβ3 integrin. PC-3 cells exhibited a 5.9% and 2.5% uptake of incubation doses of [18F]FB-PEG3-Glu-RGD-BBN within 60 min of incubation at 37°C and4°C , respectively.

Animal Studies



Positron emission tomography (PET) scans were performed after intravenous injection of 3.7 MBq (100 μCi) [18F]FB-PEG3-Glu-RGD-BBN in nude mice (n = 4) bearing PC-3 tumors at 30, 60, and 120 min (17). The estimated accumulation of [18F]FB-PEG3-Glu-RGD-BBN in the PC-3 tumors was 6.4 ± 2.5% injected dose per gram (ID/g) at 30 min; radioactivity decreased to 4.4 ± 0.7% ID/g at 1 h and 2.5 ± 0.8% ID/g at 2 h after injection. The organs with the highest radioactivity were the kidney (~4% ID/g at 60 min) and liver (<1% ID/g at 60 min). The tumor/blood, tumor/liver, tumor/kidney, and tumor/muscle ratios were 8.10, 6.43, 1.44, and 10.54, respectively. [18F]FB-PEG3-Glu-RGD-BBN exhibited higher tumor/organ ratios than [18F]FB-Glu-BBN-RGD. BBN, c(RGDyK), or BBN+c(RGDyK) were co-injected with [18F]FB-PEG3-Glu-RGD-BBN in mice bearing PC-3 tumors. Tumor accumulation at 1 h after injection (4.4% ID/g) was only partially inhibited by either BBN (65% inhibition) or RGD (50% inhibition) alone. However, BBN+RGD reduced the tumor accumulation to the background level (90% inhibition). Ex vivo biodistribution at 1 h after injection confirmed the PET imaging biodistribution analysis in the kidney, tumor, liver, and muscle but also showed high accumulation (2–4% ID/g) in the pancreas, intestine, stomach, and spleen, which possess high GRPR levels. Accumulated radioactivity in the bone was low (<0.5% ID/g).

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

R01 CA120188, R01 CA119053, R21 CA121842, R21 CA102123, P50 CA114747, U54 CA119367, R24 CA93862


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