NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

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

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

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

Show details


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

Created: ; Last Update: December 2, 2008.

Chemical name:[18F]Fluorobenzyl-bombesin[7-14]-c(RGDyK)
Abbreviated name:[18F]FB-BBN-c(RGDyK)
Agent category:Peptide
Target:Gastrin-releasing peptide receptors (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) that 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 (CNS) and the gastrointestinal (GI) system. They also act as potential growth factors for both normal and neoplastic tissues (3). Specific BBN receptors (BBN-R) have been identified on CNS and GI 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, Li et al. (17) designed a BBN-RGD heterodimer in which BBN[7-14] and c(RGDyK) were connected with a glutamate linker. N-Succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) was used to synthesize [18F]FB-BBN-RGD for tumor targeting.



[18F]SFB was added to a solution of 100 nmol BBN-RGD (17). The mixture was heated for 30 min at 60°C. The product, [18F]FB-BBN-RGD, was purified with high-performance liquid chromatography with a decay-corrected yield of 12.0 ± 0.7% (n = 4) based on [18F]SFB and a radiochemical purity of >99%. [18F]FB-BBN and [18F]FB-RGD were synthesized using the same procedure. The specific activities of [18F]FB-BBN-RGD, [18F]FB-BBN, and [18F]FB-RGD were estimated to be ~100 MBq/nmol (2.7 mCi/nmol). The log P values were -0.92, 1.49, and -1.75 for [18F]FB-BBN-RGD, [18F]FB-BBN, and [18F]FB-RGD, respectively.

In Vitro Studies: Testing in Cells and Tissues


Li et al. (17) performed in vitro inhibition studies of RGD, BBN-RGD, and FB-BBN-RGD in cultured U87MG cells with 125I-echistatin for αvβ3 integrin binding. The 50% inhibition concentration (IC50) values were 202, 428, and 282 nM, respectively. In vitro inhibition studies of BBN, BBN-RGD, and FB-BBN-RGD were also performed in cultured PC-3 cells with 125I-BBN for GRPR binding. The IC50 values were 20.7, 35.7, and 32 nM, respectively. Therefore, the BBN-RGD heterodimer exhibited comparable binding affinities for αvβ3 integrin with GRPR as the corresponding monomer. PC-3 cells express a high level of GRPR and a moderate level of αvβ3 integrin. PC-3 cells exhibited a 7% and 5% uptake of incubation dose of [18F]FB-BBN and [18F]FB-BBN-RGD within 30 min of incubation, respectively. On the other hand, PC-3 cells had low uptake of [18F]FB-RGD (<0.5%).

Animal Studies



Positron emission tomography analysis was performed after intravenous injection of 3.7 MBq (100 μCi) [18F]FB-BBN-RGD, [18F]FB-BBN, or [18F]FB-RGD in nude mice bearing PC-3 tumors (17). The estimated accumulation of [18F]FB-BBN-RGD in the PC-3 tumors was 5.0% injected dose per gram (ID/g) at 30 min and decreased to 3.6% ID/g at 1 h and 2.8% ID/g at 2 h after injection. These tumor uptakes were significantly higher than those for the corresponding monomers and their sum together (P < 0.01). The organs with the highest radioactivity were the kidney and liver. [18F]FB-BBN-RGD exhibited higher tumor/organ ratios than the monomers. BBN, c(RGDyK), or BBN+c(RGDyK) were co-injected with [18F]FB-BBN-RGD in mice bearing PC-3 tumors. Tumor accumulation at 1 h after injection (3.6% ID/g) was only partially inhibited by either BBN (1.4% ID/g) or RGD (1.8% ID/g) alone. However, BBN+RGD reduced the tumor accumulation to the background level (0.8% ID/g). Even though the αvβ3 integrin expression is weak on PC-3 cells, the specific tumor accumulation of [18F]FB-BBN-RGD was strong because of expression of αvβ3 integrin on activated endothelial cells surrounding the PC-3 tumor. Accumulated radioactivity in the bone was low.

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


Gonzalez N. , Moody T.W. , Igarashi H. , Ito T. , Jensen R.T. Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. Curr Opin Endocrinol Diabetes Obes. 2008;15(1):58–64. [PMC free article: PMC2631407] [PubMed: 18185064]
Bertaccini G. Active polypeptides of nonmammalian origin. Pharmacol Rev. 1976;28(2):127–77. [PubMed: 794887]
Chung D.H. , Evers B.M. , Beauchamp R.D. , Upp J.R. Jr, Rajaraman S. , Townsend C.M. Jr, Thompson J.C. Bombesin stimulates growth of human gastrinoma. Surgery. 1992;112(6):1059–65. [PubMed: 1455308]
Benya R.V. , Kusui T. , Pradhan T.K. , Battey J.F. , Jensen R.T. Expression and characterization of cloned human bombesin receptors. Mol Pharmacol. 1995;47(1):10–20. [PubMed: 7838118]
Reubi J.C. , Wenger S. , Schmuckli-Maurer J. , Schaer J.C. , Gugger M. Bombesin receptor subtypes in human cancers: detection with the universal radioligand (125)I-[D-TYR(6), beta-ALA(11), PHE(13), NLE(14)] bombesin(6-14) Clin Cancer Res. 2002;8(4):1139–46. [PubMed: 11948125]
Smith C.J. , Volkert W.A. , Hoffman T.J. Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes. Nucl Med Biol. 2005;32(7):733–40. [PubMed: 16243649]
Hynes R.O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992;69(1):11–25. [PubMed: 1555235]
Jin H. , Varner J. Integrins: roles in cancer development and as treatment targets. Br J Cancer. 2004;90(3):561–5. [PMC free article: PMC2410157] [PubMed: 14760364]
Varner J.A. , Cheresh D.A. Tumor angiogenesis and the role of vascular cell integrin alphavbeta3. Important Adv Oncol. 1996:69–87. [PubMed: 8791129]
Wilder R.L. Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Suppl 2Ann Rheum Dis. 2002;61:ii96–9. [PMC free article: PMC1766704] [PubMed: 12379637]
Grzesik W.J. Integrins and bone--cell adhesion and beyond. Arch Immunol Ther Exp (Warsz) 1997;45(4):271–5. [PubMed: 9523000]
Kumar C.C. Integrin alpha v beta 3 as a therapeutic target for blocking tumor-induced angiogenesis. Curr Drug Targets. 2003;4(2):123–31. [PubMed: 12558065]
Ruegg C. , Dormond O. , Foletti A. Suppression of tumor angiogenesis through the inhibition of integrin function and signaling in endothelial cells: which side to target? Endothelium. 2002;9(3):151–60. [PubMed: 12380640]
Kerr J.S. , Mousa S.A. , Slee A.M. Alpha(v)beta(3) integrin in angiogenesis and restenosis. Drug News Perspect. 2001;14(3):143–50. [PubMed: 12819820]
Mousa S.A. alphav Vitronectin receptors in vascular-mediated disorders. Med Res Rev. 2003;23(2):190–9. [PubMed: 12500288]
Haubner R. , Wester H.J. Radiolabeled tracers for imaging of tumor angiogenesis and evaluation of anti-angiogenic therapies. Curr Pharm Des. 2004;10(13):1439–55. [PubMed: 15134568]
Li Z.B. , Wu Z. , Chen K. , Ryu E.K. , Chen X. 18F-labeled BBN-RGD heterodimer for prostate cancer imaging. J Nucl Med. 2008;49(3):453–61. [PubMed: 18287274]


Search MICAD

Limit my Search:

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...