7,358
Views
80
CrossRef citations to date
0
Altmetric
Review

Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

, , &
Pages 1055-1073 | Received 29 Jan 2016, Accepted 02 Mar 2016, Published online: 28 Mar 2016

References

  • Jensen RT, Battey JF, Spindel ER, et al. International union of pharmacology. LVIII. Mammalian bombesin receptors: nomenclature, distribution, pharmacology, signaling and functions in normal and disease states. Pharmacol Rev. 2008;60:1–42.
  • Ramos-Alvarez I, Moreno P, Mantey SA, et al. Insights into bombesin receptors and ligands: highlighting recent advances. Peptides. 2015;72:128–144.
  • Gonzalez N, Moody TW, Igarashi H, et al. Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. Curr Opin Endocrinol Diabetes Obes. 2008;15:58–64.
  • Majumdar ID, Weber HC. Biology of mammalian bombesin-like peptides and their receptors. Curr Opin Endocrinol Diabetes Obes. 2011;18:68–74.
  • Gonzalez N, Moreno P, Jensen RT. Bombesin receptor -subtype 3 as a potential target for obesity and diabetes. Exp Opin Ther Targets. 2015;19:1153–1170.
  • Uehara H, Gonzalez N, Sancho V, et al. Pharmacology and selectivity of various natural and synthetic bombesin related peptide agonists for human and rat bombesin receptors differs. Peptides. 2011;32:1685–1699.
  • Weber HC. Regulation and signaling of human bombesin receptors and their biological effects. Curr Opin Endocrinol Diabetes Obes. 2009;16:66–71.
  • Sayegh AI. The role of bombesin and bombesin-related peptides in the short-term control of food intake. Prog Mol Biol Transl Sci. 2013;114:343–370.
  • Weber HC. Gastrointestinal peptides and itch sensation. Curr Opin Endocrinol Diabetes Obes. 2015;22:29–33.
  • Cornelio DB, De Farias CB, Prusch DS, et al. Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells. Mol Clin Oncol. 2013;1:148–152.
  • Petronilho F, Danielski LG, Roesler R, et al. Gastrin-releasing peptide as a molecular target for inflammatory diseases: an update. Inflamm Allergy Drug Targets. 2013;12:172–177.
  • Yu Z, Ananias HJ, Carlucci G, et al. An update of radiolabeled bombesin analogs for gastrin-releasing peptide receptor targeting. Curr Pharm Des. 2013;19:3329–3341.
  • Varshney R, Hazari PP, Fernandez P, et al. (68)Ga-labeled bombesin analogs for receptor-mediated imaging. Recent Results Cancer Res. 2013;194:221–256.
  • Wang LH, Coy DH, Taylor JE, et al. Desmethionine alkylamide bombesin analogs: a new class of bombesin receptor antagonists with potent antisecretory activity in pancreatic acini and antimitotic activity in Swiss 3T3 cells. Biochemistry (Mosc). 1990;29(3):616–622.
  • Wang LH, Coy DH, Taylor JE, et al. Des-Met carboxyl-terminally modified analogues of bombesin function as potent bombesin receptor antagonists, partial agonists, or agonists. J Biol Chem. 1990;265(26):15695–15703.
  • Sancho V, Di Florio A, Moody TW, et al. Bombesin receptor-mediated imaging and cytotoxicity: review and current status. Curr Drug Deliv. 2011;8:79–134.
  • Gonzalez N, Mantey SA, Pradhan TK, et al. Characterization of putative GRP- and NMB-receptor antagonist’s interaction with human receptors. Peptides. 2009;30:1473–1486.
  • Heinz-Erian P, Coy DH, Tamura M, et al. [D-Phe12]bombesin analogues: a new class of bombesin receptor antagonists. Am J Physiol. 1987;252:G439–G442.
  • Coy DH, Taylor JE, Jiang NY, et al. Short-chain pseudopeptide bombesin receptor antagonists with enhanced binding affinities for pancreatic acinar and Swiss 3T3 cells display strong antimitotic activity. J Biol Chem. 1989;264:14691–14697.
  • Von Schrenck T, Wang LH, Coy DH, et al. Potent bombesin receptor antagonists distinguish receptor subtypes. Am J Physiol. 1990;259:G468–G473.
  • Moreno P, Mantey SA, Nuche-Berenguer B, et al. Comparative pharmacology of bombesin receptor subtype-3, nonpeptide agonist MK-5046, a universal peptide agonist, and peptide antagonist Bantag-1 for human bombesin receptors. J Pharmacol Exp Ther. 2013;347:100–116.
  • Pradhan TK, Katsuno T, Taylor JE, et al. Identification of a unique ligand which has high affinity for all four bombesin receptor subtypes. Eur J Pharmacol. 1998;343:275–287.
  • Reubi JC, Wenger S, Schumuckli-Maurer J, et al. Bombesin receptor subtypes in human cancers: detection with the universal radoligand (125)I-[D-TYR(6), beta-ALA(11),PHE(13), NLE(14)] bombesin(6-14). Clin Cancer Res. 2002;8:1139–1146.
  • Moody TW, Moreno P, Jensen RT, Neuropeptides as lung cancer growth factors. Peptides. 2015;72:106–111.
  • Moody TW, Chan D, Fahrenkrug J, et al. Neuropeptides as autocrine growth factors in cancer cells. Curr Pharm Des. 2003;9:495–509.
  • Schulz S, Rocken C, Schulz S. Immunohistochemical detection of bombesin receptor subtypes GRP-R and BRS-3 in human tumors using novel antipeptide antibodies. Virchows Arch. 2006;449:421–427.
  • Jensen JA, Carroll RE, Benya RV. The case for gastrin-releasing peptide acting as a morphogen when it and its receptor are aberrantly expressed in cancer. Peptides. 2001;22:689–699.
  • Moody TW, Nuche-Berenguer B, Nakamura T, et al. EGFR transactivation by peptide G protein-coupled receptors in cancer. Curr Drug Targets. 2016;17(5):520–528.
  • Moody TW, Berna MJ, Mantey S, et al. Neuromedin B receptors regulate EGF receptor tyrosine phosphorylation in lung cancer cells. Eur J Pharmacol. 2010;637:38–45.
  • Sotomayor S, Munoz-Moreno L, Carmena MJ, et al. Regulation of HER expression and transactivation in human prostate cancer cells by a targeted cytotoxic bombesin analog (AN-215) and a bombesin antagonist (RC-3095). Int J Cancer. 2010;127:1813–1822.
  • Thomas SM, Grandis JR, Wentzel AL, et al. Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor receptor in lung cancer cells. Neoplasia. 2005;7:426–431.
  • Hohla F, Schally AV. Targeting gastrin releasing peptide receptors: new options for the therapy and diagnosis of cancer. Cell Cycle. 2010;9:1738–1741.
  • Cuttitta F, Carney DN, Mulshine J, et al. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer cells. Nature. 1985;316:823–826.
  • De Farias CB, Stertz L, Lima RC, et al. Reduced NGF secretion by HT-29 human colon cancer cells treated with a GRPR antagonist. Protein Pept Lett. 2009;16:650–652.
  • Jia Y, Shi H, Fan D. Significance of gastrin-releasing peptide in ovarian cancer ES2 cells. Oncol Lett. 2015;10:359–363.
  • Moody TW, Jensen RT, Garcia L, et al. Nonpeptide neuromedin B receptor antagonists inhibit the proliferation of C6 cells. Eur J Pharmacol. 2000;409:133–142.
  • Rick FG, Buchholz S, Schally AV, et al. Combination of gastrin-releasing peptide antagonist with cytotoxic agents produces synergistic inhibition of growth of human experimental colon cancers. Cell Cycle. 2012;11:2518–2525.
  • De Oliveira MS, Cechim G, Braganhol E, et al. Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models. J Neurooncol. 2009;93:191–201.
  • Rellinger EJ, Romain C, Choi S, et al. Silencing gastrin-releasing peptide receptor suppresses key regulators of aerobic glycolysis in neuroblastoma cells. Pediatr Blood Cancer. 2015;62:581–586.
  • Hong S-K, Yang S-Y, Yin S-H, et al. RC-3095, a gastrin-releasing peptide receptor antagonist, synergizes with gemcitabine to inhibit the growth of human pancreatic cancer CFPAC-1 in vitro and in vivo. Pancreas. 2014;43:15–21.
  • Xu Y, Jiang YF, Wu B. New agonist- and antagonist-based treatment approaches for advanced prostate cancer. J Int Med Res. 2012;40:1217–1226.
  • Zhang Q, Bhola NE, Lui VW, et al. Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer. Mol Cancer Ther. 2007;6:1414–1424.
  • Rick FG, Bi-Chaker A, Szalontay L, et al. Shrinkage of experimental benign prostatic hyperplasia and reduction of prostatic cell volume by a gastrin-releasing peptide antagonist. Proc Natl Acad Sci U S A. 2013;110:2617–2622.
  • Moody TW, Nakagawa T, Kang Y, et al. Bombesin/gastrin-releasing peptide receptor antagonists increase the ability of histone deacetylase inhibitors to reduce lung cancer proliferation. J Mol Neurosci. 2006;28:231–238.
  • Marostica LL, De Barros AL, Silva JO, et al. Feasibility study with 99mTc-HYNIC-betaAla-Bombesin(7-14) as an agent to early visualization of lung tumour cells in nude mice. Nucl Med Commun. 2016;27:(4):372–376.
  • Langer DA, Kautzman D, Kane MA. Inhibition of proliferation of human small cell lung cancer cells expressing an autocrine system for gastrin releasing peptide by antisense oligodeoxynucleotides to gastrin releasing peptide receptor. Lung Cancer. 2002;36:235–242.
  • Fang J, Lu Y, Ouyang K, et al. Specific antibodies elicited by a novel DNA vaccine targeting gastrin-releasing peptide inhibit murine melanoma growth in vivo. Clin Vaccine Immunol. 2009;16:1033–1039.
  • Schwartsmann G, DiLeone LP, Horowitz M, et al. A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies. Invest New Drugs. 2006;24:403–412.
  • Kelley MJ, Linnoila RI, Avis IL, et al. Antitumor activity of a monoclonal antibody directed against gastrin-releasing peptide in patients with small cell lung cancer. Chest. 1997;112:256–261.
  • Kwekkeboom DJ, Krenning EP, Peptide receptor radionuclide therapy in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am. 2016;30:179–191.
  • Ruszniewski P 177Lu-DOTATATE significantly improves progession free survival in patients with mid-gut neuroendocrine tumors: results of the phase 111 NETTER-1 trial. European Cancer Conference, 2015, abstracts. Abstract LBA6, presented at the European Cancer Conference, 2015 (abstract)
  • Sancho V, Moody TW, Mantey SA, et al. Pharmacology of putative selective hBRS-3 receptor agonists for human bombesin receptors (BnR): affinities, potencies and selectivity in multiple native and BnR transfected cells. Peptides. 2010;31:1569–1578.
  • Benya RV, Fathi Z, Battey JF, et al. Serines and threonines in the gastrin-releasing peptide receptor carboxyl terminus mediate internalization. J Biol Chem. 1993;268:20285–20290.
  • Benya RV, Kusui T, Battey JF, et al. Desensitizaton of neuromedin B receptors (NMB-R) on native and NMB-R transfected cells involves down-regulation and internalization. J Biol Chem. 1994;269:11721–11728.
  • Benya RV, Fathi Z, Pradhan T, et al. Gastrin-releasing peptide receptor-induced internalization, down-regulation, desensitization and growth: possible role of cAMP. Mol Pharmacol. 1994;46(2):235–245.
  • Mansi R, Abiraj K, Wang X, et al. Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors. J Med Chem. 2015;58:682–691.
  • Cescato R, Maina T, Nock B, et al. Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J Nucl Med. 2008;49:318–326.
  • Ginj M, Zhang H, Waser B, et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci U S A. 2006;103:16436–16441.
  • Abiraj K, Mansi R, Tamma M-L, et al. Bombesin antagonist-based radioligands for translational nuclear imaging of gastrin-releasing peptide receptor-positive tumors. J Nucl Med. 2011;52:1970–1978.
  • Chatalic KL, Franssen GM, Van Weerden WM, et al. Preclinical comparison of Al18F- and 68Ga-labeled gastrin-releasing peptide receptor antagonists for PET imaging of prostate cancer. J Nucl Med. 2014;55:2050–2056.
  • Gourni E, Mansi R, Jamous M, et al. N-terminal modifications improve the receptor affinity and pharmacokinetics of radiolabeled peptidic gastrin-releasing peptide receptor antagonists: examples of 68Ga- and 64Cu-labeled peptides for PET imaging. J Nucl Med. 2014;55:1719–1725.
  • Maina T, Bergsma H, Kulkarni HR, et al. Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [Ga]SB3 and PET/CT. Eur J Nucl Med Mol Imaging. 2015. (In press)
  • Stott Reynolds TJ, Schehr R, Liu D, et al. Characterization and evaluation of DOTA-conjugated Bombesin/RGD-antagonists for prostate cancer tumor imaging and therapy. Nucl Med Biol. 2015;42:99–108.
  • Varasteh Z, Aberg O, Velikyan I, et al. In vitro and in vivo evaluation of a (18)F-labeled high affinity NOTA conjugated bombesin antagonist as a PET ligand for GRPR-targeted tumor imaging. PLoS ONE. 2013;8:e81932.
  • Durkan K, Jiang Z, Rold TL, et al. A heterodimeric [RGD-Glu-[(64)Cu-NO2A]-6-Ahx-RM2] alphavbeta3/GRPr-targeting antagonist radiotracer for PET imaging of prostate tumors. Nucl Med Biol. 2014;41:133–139.
  • Scopinaro F, Di Santo GP, Tofani A, et al. Fast cancer uptake of 99mTc-labelled bombesin (99mTc BN1). In Vivo. 2005;19:1071–1076.
  • Scopinaro F, De Vincentis G, Corazziari E, et al. Detection of colon cancer with 99mTc-labeled bombesin derivative (99mTc-leu13-BN1). Cancer Biother Radiopharm. 2004;19:245–252.
  • De Vincentis G, Scopinaro F, Varvarigou A, et al. Phase I trial of technetium [Leu13] bombesin as cancer seeking agent: possible scintigraphic guide for surgery? Tumori. 2002;88:S28–S30.
  • Scopinaro F, Varvarigou AD, Ussof W, et al. Technetium labeled bombesin-like peptide: preliminary report on breast cancer uptake in patients. Cancer Biother Radiopharm. 2002;17:327–335.
  • Soluri A, Scopinaro F, De Vincentis G, et al. 99MTC [13LEU] bombesin and a new gamma camera, the imaging probe, are able to guide mammotome breast biopsy. Anticancer Res. 2003;23:2139–2142.
  • Scopinaro F, De Vincentis G, Varvarigou AD, et al. 99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes. Eur J Nucl Med Mol Imaging. 2003;30:1378–1382.
  • De Vincentis G, Remediani S, Varvarigou AD, et al. Role of 99mTc-bombesin scan in diagnosis and staging of prostate cancer. Cancer Biother Radiopharm. 2004;19:81–84.
  • Santos-Cuevas CL, Ferro-Flores G, Arteaga De Murphy C, et al. Targeted imaging of gastrin-releasing peptide receptors with 99mTc-EDDA/HYNIC-[Lys3]-bombesin: biokinetics and dosimetry in women. Nucl Med Commun. 2008;29:741–747.
  • Van de Wiele C, Dumont F, Vanden Broecke R, et al. Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study. Eur J Nucl Med. 2000;27:1694–1699.
  • Van de Wiele C, Dumont F, Dierck RA, et al. Biodistribution and dosimetry of (99m)Tc-RP527, a gastrin-releasing peptide (GRP) agonist for the visualization of GRP receptor-expressing malignancies. J Nucl Med. 2001;42:1722–1727.
  • Van de Wiele C, Phonteyne P, Pauwels P, et al. Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry. J Nucl Med. 2008;49:260–264.
  • Chen Q, Ma Q, Chen M, et al. An exploratory study on 99mTc-RGD-BBN peptide scintimammography in the assessment of breast malignant lesions compared to 99mTc-3P4-RGD2. PLoS ONE. 2015;10:e0123401.
  • Ji T, Sun Y, Chen B, et al. The diagnostic role of 99mTc-dual receptor targeted probe and targeted peptide bombesin (RGD-BBN) SPET/CT in the detection of malignant and benign breast tumors and axillary lymph nodes compared to ultrasound. Hell J Nucl Med. 2015;18:108–113.
  • Mather SJ, Nock BA, Maina T, et al. GRP receptor imaging of prostate cancer using [(99m)Tc]Demobesin 4: a first-in-man study. Mol Imaging Biol. 2014;16:888–895.
  • Ananias HJ, Yu Z, Hoving HD, et al. Application of (99m)Technetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) SPECT/CT in prostate cancer patients: a first-in-man study. Nucl Med Biol. 2013;40:933–938.
  • Shariati F, Aryana K, Fattahi A, et al. Diagnostic value of 99mTc-bombesin scintigraphy for differentiation of malignant from benign breast lesions. Nucl Med Commun. 2014;35:620–625.
  • Dimitrakopoulou-Strauss A, Hohenberger P, Haberkorn U, et al. 68Ga-labeled bombesin studies in patients with gastrointestinal stromal tumors: comparison with 18F-FDG. J Nucl Med. 2007;48:1245–1250.
  • Seiz M, Dimitrakopoulou-Strauss A, Schubert GA, et al. Differentiation between malignant transformation and tumour recurrence by (68)Ga-bombesin and (18)F-FDG-PET, in patients with low grade gliomas. Hell J Nucl Med. 2008;11:149–152.
  • Dimitrakopoulou-Strauss A, Seiz M, Tuettenberg J, et al. Pharmacokinetic studies of Ga-labeled Bombesin (Ga-BZH) and F-18 FDG PET in patients with recurrent gliomas and comparison to grading: preliminary results. Clin Nucl Med. 2011;36:101–108.
  • Strauss LG, Koczan D, Seiz M, et al. Correlation of the Ga-68-bombesin analog Ga-68-BZH3 with receptors expression in gliomas as measured by quantitative dynamic positron emission tomography (dPET) and gene arrays. Mol Imaging Biol. 2012;14:376–383.
  • Kahkonen E, Jambor I, Kemppainen J, et al. In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548. Clin Cancer Res. 2013;19:5434–5443.
  • Minamimoto R, Hancock S, Schneider B, et al. Pilot comparison of 68Ga-RM2 PET and 68Ga-PSMA PET in patients with biochemically recurrent prostate cancer. J Nucl Med. 2015. (in press).
  • Zhang J, Li D, Lang L, et al. 68Ga-NOTA-Aca-BBN(7-14) PET/CT in healthy volunteers and glioma patients. J Nucl Med. 2016;57:9–14.
  • Wieser G, Mansi R, Grosu AL, et al. Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist–from mice to men. Theranostics. 2014;4:412–419.
  • Sah B-R, Burger IA, Schibli R, et al. Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer. J Nucl Med. 2015;56:372–378.
  • Ma L, Yu P, Veerendra B, et al. In vitro and in vivo evaluation of Alexa Fluor 680-bombesin[7-14]NH2 peptide conjugate, a high-affinity fluorescent probe with high selectivity for the gastrin-releasing peptide receptor. Mol Imaging. 2007;6:171–180.
  • Cai Q-Y, Yu P, Besch-Williford C, et al. Near-infrared fluorescence imaging of gastrin releasing peptide receptor targeting in prostate cancer lymph node metastases. Prostate. 2013;73:842–854.
  • Chen H, Wan S, Zhu F, et al. A fast tumor-targeting near-infrared fluorescent probe based on bombesin analog for in vivo tumor imaging. Contrast Media Mol Imaging. 2014;9:122–134.
  • Heidari Z, Sariri R, Salouti M. Gold nanorods-bombesin conjugate as a potential targeted imaging agent for detection of breast cancer. J Photochem Photobiol B. 2014;130:40–46.
  • Jafari A, Salouti M, Shayesteh SF, et al. Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI. Nanotechnology. 2015;26:075101.
  • Martin AL, Hickey JL, Ablack AL, et al. Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells. J Nanopart Res. 2009;12:1599–1608.
  • Lee C-M, Jeong H-J, Cheong S-J, et al. Prostate cancer-targeted imaging using magnetofluorescent polymeric nanoparticles functionalized with bombesin. Pharm Res. 2010;27:712–721.
  • Bandari RP, Jiang Z, Reynolds TS, et al. Synthesis and biological evaluation of copper-64 radiolabeled [DUPA-6-Ahx-(NODAGA)-5-Ava-BBN(7-14)NH2], a novel bivalent targeting vector having affinity for two distinct biomarkers (GRPr/PSMA) of prostate cancer. Nucl Med Biol. 2014;41:355–363.
  • Cui L, Liu Z, Jin X, et al. Evaluation of 188Re-MAG2-RGD-bombesin for potential prostate cancer therapy. Nucl Med Biol. 2013;40:182–189.
  • Jackson AB, Nanda PK, Rold TL, et al. 64Cu-NO2A-RGD-Glu-6-Ahx-BBN(7-14)NH2: a heterodimeric targeting vector for positron emission tomography imaging of prostate cancer. Nucl Med Biol. 2012;39:377–387.
  • Jiang L, Miao Z, Liu H, et al. 177Lu-labeled RGD-BBN heterodimeric peptide for targeting prostate carcinoma. Nucl Med Commun. 2013;34:909–914.
  • Liu Z, Niu G, Wang F, et al. (68)Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging. Eur J Nucl Med Mol Imaging. 2009;36:1483–1494.
  • Liu Z, Li Z-B, Cao Q, et al. Small-animal PET of tumors with (64)Cu-labeled RGD-bombesin heterodimer. J Nucl Med. 2009;50:1168–1177.
  • Aranda-Lara L, Ferro-Flores G, Ramirez FM, et al. Improved radiopharmaceutical based on 99mTc-Bombesin-folate for breast tumour imaging. Nucl Med Commun. 2016;37(4):377–386.
  • Marsouvanidis PJ, Melis M, De Blois E, et al. In vivo enzyme inhibition improves the targeting of [177Lu]DOTA-GRP(13-27) in GRPR-positive tumors in mice. Cancer Biother Radiopharm. 2014;29:359–367.
  • Reynolds TS, Bandari RP, Jiang Z, et al. Lutetium-177 labeled bombesin peptides for radionuclide therapy. Curr Radiopharm. 2016;9:33–43.
  • Schroeder RP, Van Weerden WM, Bangma C, et al. Peptide receptor imaging of prostate cancer with radiolabelled bombesin analogues. Methods. 2009;48:200–204.
  • Mukai H, Wada Y, Watanabe Y. The synthesis of 64Cu-chelated porphyrin photosensitizers and their tumor-targeting peptide conjugates for the evaluation of target cell uptake and PET image-based pharmacokinetics of targeted photodynamic therapy agents. Ann Nucl Med. 2013;27:625–639.
  • Dubuc C, Langlois R, Benard F, et al. Targeting gastrin-releasing peptide receptors of prostate cancer cells for photodynamic therapy with a phthalocyanine-bombesin conjugate. Bioorg Med Chem Lett. 2008;18:2424–2427.
  • Sioud M, Mobergslien A. Efficient siRNA targeted delivery into cancer cells by gastrin-releasing peptides. Bioconjug Chem. 2012;23:1040–1049.
  • Safavy A, Raisch KP, Khazaeli MB, et al. Paclitaxel derivatives for targeted therapy of cancer: toward the development of smart taxanes. J Med Chem. 1999;42:4919–4924.
  • Moody TW, Mantey SA, Pradhan TK, et al. Development of high affinity camptothecin-bombesin conjugates that have targeted cytotoxicity for bombesin receptor-containing tumor cells. J Biol Chem. 2004;279:23580–23589.
  • Moody TW, Sun L-C, Mantey SA, et al. In vitro and in vivo antitumor effects of cytotoxic camptothecin-bombesin conjugates are mediated by specific interaction with cellular bombesin receptors. J Pharmacol Exp Ther. 2006;318:1265–1272.
  • Wang C, Sun X, Wang K, et al. Breast cancer targeted chemotherapy based on doxorubicin-loaded bombesin peptide modified nanocarriers. Drug Deliv. 2015. (in press).
  • Moody TW, Pradhan T, Mantey SA, et al. Bombesin marine toxin conjugates inhibit the growth of lung cancer cells. Life Sci. 2008;82:855–861.
  • Liu S, Yang H, Wan L, et al. Enhancement of cytotoxicity of antimicrobial peptide magainin II in tumor cells by bombesin-targeted delivery. Acta Pharmacol Sin. 2011;32:79–88.
  • Sioud M, Mobergslien A. Selective killing of cancer cells by peptide-targeted delivery of an anti-microbial peptide. Biochem Pharmacol. 2012;84:1123–1132.
  • Yang H, Cai H, Wan L, et al. Bombesin analogue-mediated delivery preferentially enhances the cytotoxicity of a mitochondria-disrupting peptide in tumor cells. PLoS ONE. 2013;8:e57358.
  • vanderSpek JC, Sutherland JA, Zeng H, et al. Inhibition of protein synthesis in small cell lung cancer cells induced by the diphtheria toxin-related fusion protein DAB389 GRP. Cancer Res. 1997;57:290–294.
  • Zhou J, Chen J, Zhong R, et al. Targeting gastrin-releasing peptide receptors on small cell lung cancer cells with a bispecific molecule that activates polyclonal T lymphocytes. Clin Cancer Res. 2006;12:2224–2231.
  • De Barros AL, Mota L, Soares DC, et al. Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification. Bioorg Med Chem Lett. 2011;21:7373–7375.
  • Accardo A, Salsano G, Morisco A, et al. Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent. Int J Nanomedicine. 2012;7:2007–2017.
  • Accardo A, Aloj L, Aurilio M, et al. Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs. Int J Nanomedicine. 2014;9:1537–1557.
  • Accardo A, Mansi R, Salzano G, et al. Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells. J Drug Target. 2013;21:240–249.
  • De Barros AL, Mota L, Soares DC, et al. Long-circulating, pH-sensitive liposomes versus long-circulating, non-pH-sensitive liposomes as a delivery system for tumor identification. J Biomed Nanotechnol. 2013;9:1636–1643.
  • Accardo A, Mansi R, Morisco A, et al. Peptide modified nanocarriers for selective targeting of bombesin receptors. Mol Biosyst. 2010;6:878–887.
  • Chang Y-J, Yu C-Y, Hsu C-W, et al. Molecular imaging and therapeutic efficacy of 188Re-(DXR)-liposome-BBN in AR42J pancreatic tumor-bearing mice. Oncol Rep. 2012;28:1736–1742.
  • Kulhari H, Pooja D, Shrivastava S, et al. Peptide conjugated polymeric nanoparticles as a carrier for targeted delivery of docetaxel. Colloids Surf B Biointerfaces. 2014;117:166–173.
  • Hosta-Rigau L, Olmedo I, Arbiol J, et al. Multifunctionalized gold nanoparticles with peptides targeted to gastrin-releasing peptide receptor of a tumor cell line. Bioconjug Chem. 2010;21:1070–1078.
  • Chanda N, Kattumuri V, Shukla R, et al. Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity. Proc Natl Acad Sci U S A. 2010;107:8760–8765.
  • Jimenez-Mancilla N, Ferro-Flores G, Santos-Cuevas C, et al. Multifunctional targeted therapy system based on (99m) Tc/(177) Lu-labeled gold nanoparticles-Tat(49-57)-Lys(3) -bombesin internalized in nuclei of prostate cancer cells. J Labelled Comp Radiopharm. 2013;56:663–671.
  • Suresh D, Zambre A, Chanda N, et al. Bombesin peptide conjugated gold nanocages internalize via clathrin mediated endocytosis. Bioconjug Chem. 2014;25:1565–1579.
  • Qiao J, Hong T, Guo H, et al. Single-walled carbon nanotube-mediated small interfering RNA delivery for gastrin-releasing peptide receptor silencing in human neuroblastoma. Methods Mol Biol. 2013;1026:137–147.
  • Qiao J, Hong T, Triana TS, et al. Magneto-fluorescent carbon nanotube-mediated siRNA for gastrin-releasing peptide receptor silencing in neuroblastoma. RSC Adv. 2013;3:4544–4551.
  • Dalm SU, Martens JW, Sieuwerts AM, et al. In vitro and in vivo application of radiolabeled gastrin-releasing peptide receptor ligands in breast cancer. J Nucl Med. 2015;56:752–757.
  • Gugger M, Reubi JC. Gastrin-releasing peptide receptors in non-neoplastic and neoplastic human breast. Am J Pathol. 1999;155:2067–2076.
  • Ni C, Zhao X, Sun T, et al. Role of gastrin-releasing peptides in breast cancer metastasis. Hum Pathol. 2012;43:2342–2347.
  • Chao C, Ives K, Hellmich HL, et al. Gastrin-releasing peptide receptor in breast cancer mediates cellular migration and interleukin-8 expression. J Surg Res. 2009;156:26–31.
  • Guojun W, Wei G, Kedong O, et al. A novel vaccine targeting gastrin-releasing peptide: efficient inhibition of breast cancer growth in vivo. Endocr Relat Cancer. 2008;15:149–159.
  • Bajo AM, Schally AV, Groot K, et al. Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers. Br J Cancer. 2004;90:245–252.
  • Schally AV. New approaches to the therapy of various tumors based on Peptide analogues. Horm Metab Res. 2008;40:315–322.
  • Ait-Mohand S, Fournier P, Dumulon-Perreault V, et al. Evaluation of 64Cu-labeled bifunctional chelate-bombesin conjugates. Bioconjug Chem. 2011;22:1729–1735.
  • Liu Z, Yan Y, Liu S, et al. (18)F, (64)Cu, and (68)Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer. Bioconjug Chem. 2009;20:1016–1025.
  • Parry JJ, Andrews R, Rogers BE. MicroPET imaging of breast cancer using radiolabeled bombesin analogs targeting the gastrin-releasing peptide receptor. Breast Cancer Res Treat. 2007;18:110–117.
  • Pujatti PB, Foster JM, Finucane C, et al. Evaluation and comparison of a new DOTA and DTPA-bombesin agonist in vitro and in vivo in low and high GRPR expressing prostate and breast tumor models. Appl Radiat Isot. 2015;96:91–101.
  • Retzloff LB, Heinzke L, Figureoa SD, et al. Evaluation of [99mTc-(CO)3-X-Y-Bombesin(7-14)NH2] conjugates for targeting gastrin-releasing peptide receptors overexpressed on breast carcinoma. Anticancer Res. 2010;30:19–30.
  • De Barros AL, Mota LD, Coelho MM, et al. Bombesin encapsulated in long-circulating pH-sensitive liposomes as a radiotracer for breast tumor identification. J Biomed Nanotechnol. 2015;11:342–350.
  • Heidari Z, Salouti M, Sariri R, Breast cancer photothermal therapy based on gold nanorods targeted by covalently-coupled bombesin peptide. Nanotechnology. 2015;26:195101.
  • Engel JB, Schally AV, Halmos G, et al. Targeted cytotoxic bombesin analog AN-215 effectively inhibits experimental human breast cancers with a low induction of multi-drug resistance proteins. Endocr Relat Cancer. 2005;12:999–1009.
  • Mendoza-Sanchez AN, Ferro-Flores G, Ocampo-Garcia BE, et al. Lys3-bombesin conjugated to 99mTc-labelled gold nanoparticles for in vivo gastrin releasing peptide-receptor imaging. J Biomed Nanotechnol. 2010;6:375–384.
  • Scopinaro F, Varvarigou A, Ussof W, et al. Breast cancer takes up 99mTc bombesin. A Preliminary Report. Tumori. 2002;88:S25–S28.
  • Van de Wiele C, Dumont F, Vanden Broecke R, et al. Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study. Eur J Nucl Med. 2000;27:1694–1699.
  • Beer M, Montani M, Gerhardt J, et al. Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates. Prostate. 2012;72:318–325.
  • Markwalder R, Reubi JC. Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res. 1999;59:1152–1159.
  • Sun B, Halmos G, Schally AV, et al. Presence of receptors for bombesin/gastrin-releasing peptide and mRNA for three receptor subtypes in human prostate cancers. Prostate. 2000;42:295–303.
  • Ischia J, Patel O, Bolton D, et al. Expression and function of gastrin-releasing peptide (GRP) in normal and cancerous urological tissues. BJU Int. 2014;113 Suppl 2:40–47.
  • Korner M, Waser B, Rehmann R, et al. Early over-expression of GRP receptors in prostatic carcinogenesis. Prostate. 2014;74:217–224.
  • Schroeder RP, De Visser M, Van Weerden WM, et al. Androgen-regulated gastrin-releasing peptide receptor expression in androgen-dependent human prostate tumor xenografts. Int J Cancer. 2010;126:2826–2834.
  • Laukkanen MO, Castellone MD. Gastrin-releasing peptide receptor targeting in cancer treatment: emerging signaling networks and therapeutic applications. Curr Drug Targets. 2016;71(5):508–514.
  • Wen X, Chao C, Ives K, et al. Regulation of bombesin-stimulated cyclooxygenase-2 expression in prostate cancer cells. BMC Mol Biol. 2011;12:29.
  • Aprikian AG, Han K, Guy L, et al. Neuroendocrine differentiation and the bombesin/gastrin-releasing peptide family of neuropeptides in the progression of human prostate cancer. Prostate Suppl. 1998;8:52–61.
  • Ananias HJ, Yu Z, Dierckx RA, et al. (99m)technetium-HYNIC(tricine/TPPTS)-Aca-bombesin(7-14) as a targeted imaging agent with microSPECT in a PC-3 prostate cancer xenograft model. Mol Pharm. 2011;8:1165–1173.
  • Bergmann R, Ruffani A, Graham B, et al. Synthesis and radiopharmacological evaluation of (6)(4)Cu-labeled bombesin analogs featuring a bis(2-pyridylmethyl)-1,4,7-triazacyclononane chelator. Eur J Med Chem. 2013;70:434–446.
  • Carlucci G, Ananias HJ, Yu Z, et al. Preclinical evaluation of a novel (1)(1)(1)In-labeled bombesin homodimer for improved imaging of GRPR-positive prostate cancer. Mol Pharm. 2013;10:1716–1724.
  • Carlucci G, Kuipers A, Ananias HJ, et al. GRPR-selective PET imaging of prostate cancer using [(18)F]-lanthionine-bombesin analogs. Peptides. 2015;67:45–54.
  • Craft JM, De Silva RA, Lears KA, et al. In vitro and in vivo evaluation of a 64Cu-labeled NOTA-Bn-SCN-Aoc-bombesin analogue in gastrin-releasing peptide receptor expressing prostate cancer. Nucl Med Biol. 2012;39:609–616.
  • Varasteh Z, Velikyan I, Lindeberg G, et al. Synthesis and characterization of a high-affinity NOTA-conjugated bombesin antagonist for GRPR-targeted tumor imaging. Bioconjug Chem. 2013;24:1144–1153.
  • Dijkgraaf I, Franssen GM, McBride WJ, et al. PET of tumors expressing gastrin-releasing peptide receptor with an 18F-labeled bombesin analog. J Nucl Med. 2012;53:947–952.
  • Ho C-L, Chen L-C, Lee W-C, et al. Receptor-binding, biodistribution, dosimetry, and micro-SPECT/CT imaging of 111In-[DTPA(1), Lys(3), Tyr(4)]-bombesin analog in human prostate tumor-bearing mice. Cancer Biother Radiopharm. 2009;24:435–443.
  • Lane SR, Nanda P, Rold TL, et al. Optimization, biological evaluation and microPET imaging of copper-64-labeled bombesin agonists, [64Cu-NO2A-(X)-BBN(7-14)NH2], in a prostate tumor xenografted mouse model. Nucl Med Biol. 2010;37:751–761.
  • Mu L, Honer M, Becaud J, et al. In vitro and in vivo characterization of novel 18F-labeled bombesin analogues for targeting GRPR-positive tumors. Bioconjug Chem. 2010;21:1864–1871.
  • Schroeder RP, Van Weerden WM, Krenning EP, et al. Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts. Eur J Nucl Med Mol Imaging. 2011;38:1257–1266.
  • Schwarzenbock SM, Schmeja P, Kurth J, et al. Comparison of [C]Choline ([C]CHO) and [F]Bombesin (BAY 86-4367) as imaging probes for prostate cancer in a PC-3 prostate cancer xenograft model. Mol Imaging Biol. 2015. (in press).
  • Dumont RA, Tamma M, Braun F, et al. Targeted radiotherapy of prostate cancer with a gastrin-releasing peptide receptor antagonist is effective as monotherapy and in combination with rapamycin. J Nucl Med. 2013;54:762–769.
  • Gourni E, Del PL, Kheirallah E, et al. Copper-64 labeled macrobicyclic sarcophagine coupled to a grp receptor antagonist shows great promise for PET imaging of prostate cancer. Mol Pharm. 2015;12:2781–2790.
  • Honer M, Mu L, Stellfeld T, et al. 18F-labeled bombesin analog for specific and effective targeting of prostate tumors expressing gastrin-releasing peptide receptors. J Nucl Med. 2011;52:270–278.
  • Lim JC, Cho EH, Kim JJ, et al. Biological evaluation of (177)Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting. Nucl Med Biol. 2015;42:131–136.
  • Nanda PK, Pandey U, Bottenus BN, et al. Bombesin analogues for gastrin-releasing peptide receptor imaging. Nucl Med Biol. 2012;39:461–471.
  • Pan D, Xu YP, Yang RH, et al. A new (68)Ga-labeled BBN peptide with a hydrophilic linker for GRPR-targeted tumor imaging. Amino Acids. 2014;46:1481–1489.
  • Pourghiasian M, Liu Z, Pan J, et al. (18)F-AmBF3-MJ9: A novel radiofluorinated bombesin derivative for prostate cancer imaging. Bioorg Med Chem. 2015;23:1500–1506.
  • Schroeder RP, Muller C, Reneman S, et al. A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues. Eur J Nucl Med Mol Imaging. 2010;37:1386–1396.
  • Nanda PK, Wienhoff BE, Rold TL, et al. Positron-emission tomography (PET) imaging agents for diagnosis of human prostate cancer: agonist vs. antagonist ligands. In Vivo. 2012;26:583–592.
  • Levi J, Sathirachinda A, Gambhir SS. A high-affinity, high-stability photoacoustic agent for imaging gastrin-releasing peptide receptor in prostate cancer. Clin Cancer Res. 2014;20:3721–3729.
  • Sturzu A, Sheikh S, Echner H, et al. Rhodamine-marked bombesin: a novel means for prostate cancer fluorescence imaging. Invest New Drugs. 2014;32:37–46.
  • Prasanphanich AF, Retzloff L, Lane SR, et al. In vitro and in vivo analysis of [(64)Cu-NO2A-8-Aoc-BBN(7-14)NH(2)]: a site-directed radiopharmaceutical for positron-emission tomography imaging of T-47D human breast cancer tumors. Nucl Med Biol. 2009;36:171–181.
  • Yu Z, Carlucci G, Ananias HJ, et al. Evaluation of a technetium-99m labeled bombesin homodimer for GRPR imaging in prostate cancer. Amino Acids. 2013;44:543–553.
  • Zhou Z, Wagh NK, Ogbomo SM, et al. Synthesis and in vitro and in vivo evaluation of hypoxia-enhanced 111In-bombesin conjugates for prostate cancer imaging. J Nucl Med. 2013;54:1605–1612.
  • Rybalov M, Ananias HJ, Hoving HD, et al. PSMA, EpCAM, VEGF and GRPR as imaging targets in locally recurrent prostate cancer after radiotherapy. Int J Mol Sci. 2014;15:6046–6061.
  • Mattei J, Achcar RD, Cano CH, et al. Gastrin-releasing peptide receptor expression in lung cancer. Arch Pathol Lab Med. 2014;138:98–104.
  • Liu Z, Huang J, Dong C, et al. 99mTc-labeled RGD-BBN peptide for small-animal SPECT/CT of lung carcinoma. Mol Pharm. 2012;9:1409–1417.
  • Du J, Li L. Which one performs better for targeted lung cancer combination therapy: pre- or post-bombesin-decorated nanostructured lipid carriers?. Drug Delivery. 2015. (in press).
  • Yang H-J, Gu Y, Chen C, et al. Diagnostic value of pro-gastrin-releasing peptide for small cell lung cancer: a meta-analysis. Clin Chem Lab Med. 2011;49:1039–1046.
  • Yang D-W, Zhang Y, Hong Q-Y, et al. Role of a serum-based biomarker panel in the early diagnosis of lung cancer for a cohort of high-risk patients. Cancer. 2015;121 Suppl 17:3113–3121.
  • Korse CM, Taal BG, Bonfrer JM, et al. An elevated progastrin-releasing peptide level in patients with well-differentiated neuroendocrine tumours indicates a primary tumour in the lung and predicts a shorter survival. Ann Oncol. 2011;22:2625–2630.
  • Tang J-H, Zhang X-L, Zhang Z-H, et al. Diagnostic value of tumor marker pro-gastrin-releasing peptide in patients with small cell lung cancer: a systematic review. Chin Med J (Engl). 2011;124:1563–1568.
  • Ono A, Naito T, Ito I, et al. Correlations between serial pro-gastrin-releasing peptide and neuron-specific enolase levels, and the radiological response to treatment and survival of patients with small-cell lung cancer. Lung Cancer. 2012;76:439–444.
  • Roesler R, Schwartsmann G. Gastrin-releasing peptide receptors in the central nervous system: role in brain function and as a drug target. Front Endocrinol (Lausanne). 2012;3:159.
  • Flores DG, Meurer L, Uberti AF, et al. Gastrin-releasing peptide receptor content in human glioma and normal brain. Brain Res Bull. 2010;82:95–98.
  • Abujamra AL, Almeida VR, Brunetto AL, et al. A gastrin-releasing peptide receptor antagonist stimulates Neuro2a neuroblastoma cell growth: prevention by a histone deacetylase inhibitor. Cell Biol Int. 2009;33:899–903.
  • Kang J, Ishola TA, Baregamian N, et al. Bombesin induces angiogenesis and neuroblastoma growth. Cancer Lett. 2007;253:273–281.
  • Carroll RE, Matkowskyj KA, Chakrabarti S, et al. Abberrant expression of gastrin-releasing peptide and its receptor by well-differentiated colon cancers in humans. Am J Physiol. 1999;276:G655–G665.
  • Matusiak D, Glover S, Nathaniel R, et al. Neuromedin B and its receptor are mitogens in both normal and malignant epithelial cells lining the colon. Am J Physiol (Gastrointest Liver Physiol). 2005;288:G718–G728.
  • Zou H, Thomas SM, Yan Z-W, et al. Human rhomboid family-1 gene RHBDF1 participates in GPCR-mediated transactivation of EGFR growth signals in head and neck squamous cancer cells. Faseb J. 2009;23:425–432.
  • Hohla F, Winder T, Greil R, et al. Targeted therapy in advanced metastatic colorectal cancer: current concepts and perspectives. World J Gastroenterol. 2014;20:6102–6112.
  • Carlesso FN, Fuscaldi LL, Araujo RS, et al. Evaluation of 99mTc-HYNIC-betaAla-Bombesin(7-14) as an agent for pancreas tumor detection in mice. Braz J Med Biol Res. 2015;48:923–928.
  • Cheng C, Pan L, Dimitrakopoulou-Strauss A, et al. Comparison between 68Ga-bombesin (68Ga-BZH3) and the cRGD tetramer 68Ga-RGD4 studies in an experimental nude rat model with a neuroendocrine pancreatic tumor cell line. EJNMMI Res. 2011;1:34.
  • Shi J, Jia B, Liu Z, et al. 99mTc-labeled bombesin(7-14)NH2 with favorable properties for SPECT imaging of colon cancer. Bioconjug Chem. 2008;19:1170–1178.
  • Keller G, Schally AV, Nagy A, et al. Targeted chemotherapy with cytotoxic bombesin analogue AN-215 can overcome chemoresistance in experimental renal cell carcinomas. Cancer. 2005;104:2266–2274.
  • Van Vliet EI, Teunissen JJ, Kam BL, et al. Treatment of gastroenteropancreatic neuroendocrine tumors with peptide receptor radionuclide therapy. Neuroendocrinology. 2013;97:74–85.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.