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68Ga-Labeled Bombesin Analogs for Receptor-Mediated Imaging

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Book cover Theranostics, Gallium-68, and Other Radionuclides

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 194))

Abstract

Targeted receptor-mediated imaging techniques have become crucial tools in present targeted diagnosis and radiotherapy as they provide accurate and specific diagnosis of disease information. Peptide-based pharmaceuticals are gaining popularity, and there has been vast interest in developing 68Ga-labeled bombesin (Bn) analogs. The gastrin-releasing peptide (GRP) family and its Bn analog have been implicated in the biology of several human cancers. The three bombesin receptors GRP, NMB, and BRS-3 receptor are most frequently ectopically expressed by common, important malignancies. The low expression of Bn/GRP receptors in normal tissue and relatively high expression in a variety of human tumors can be of biological importance and form a molecular basis for Bn/GRP receptor-mediated imaging. To develop a Bn-like peptide with favorable tumor targeting and pharmacokinetic characteristics for possible clinical use, several modifications in the Bn-like peptides, such as the use of a variety of chelating agents, i.e., acyclic and macrocyclic agents with different spacer groups and with different metal ions (gallium), have been performed in recent years without significant disturbance of the vital binding scaffold. The favorable physical properties of 68Ga, i.e., short half-life, and the fast localization of small peptides make this an ideal combination to study receptor-mediated imaging in patients.

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Abbreviations

Ac:

Acetyl

Aca:

Aminohexanoic acid

ACMpip:

4-Aminocarboxymethylpiperidine

AMBA:

Aminobenzoyl

Bn/BBN:

Bombesin

BRS-3:

Bombesin receptor subtype 3

Bzdig:

p-aminobenzyldiglycolic acid

BZH3 :

[DTyr6,βAla11,Thi13,Nle14]Bn(6–14)

Cha:

Cyclohexylalanine

DOTA:

1,4,7,10-Triazacyclododecanetetraacetic acid

DTPA:

Diethylenetriaminepentaacetic acid

Des-Met:

Methionine removed

FA01010:

(4R,5S)-4-Amino-5-methylheptanoic acid

GRP:

Gastrin-releasing peptide

GRP-R/GRPR:

Gastrin-releasing peptide receptor

GPR-R/GPRR:

G-protein receptor

Ga:

Gallium

GI:

Gastrointestinal

mIP:

meta-phenylalanine

MBq:

Megabecquerel

NHEt:

Et = ethyl

NMB:

Neuromedin B

NMBR:

Neuromedin B receptor

NOTA:

1,4,7-Triazacyclononanetriacetic acid

PEG2:

(2-Aminoethyl)-carboxymethyl ether

PEG4:

15-Amino-4,7,10,13-tetraoxapentadecanoic acid

PET:

Positron emission tomography

RM1:

H-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2

RGD:

(Arginine-glycine-aspartic acid)

SPECT:

Single-photon emission computed tomography

Sta:

Statine: (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid

Tha:

β-(2-Thienyl) alanine

Thi:

3-(2-Thienyl) alanine

Tpi:

2,3,4,9-Tetrahydro-1H-pyridol[3,4-b]indol-3-carboxylic acid

References

  • Abd-Elgaliel WR, Gallazzi F, Garrison JC et al (2008) Design, synthesis, and biological evaluation of an antagonist bombesin analog as targeting vector. Bioconjug Chem 19:2040–2048

    PubMed  CAS  Google Scholar 

  • Abiraj K, Jaccard H, Kretzschmar M et al (2008) Novel DOTA-based prochelator for divalent peptide vectorization: synthesis of dimeric bombesin analogs for multimodality tumor imaging and therapy. Chem Commun (Camb) 28(28):3248–3250

    Google Scholar 

  • Abiraj K, Mansi R, Tamma ML et al (2010) Tetraamine-derived bifunctional chelators for technetium-99m labeling: synthesis, bioconjugation and evaluation as targeted SPECT imaging probes for GRP-receptor-positive tumors. Chemistry 16:2115–2124

    PubMed  CAS  Google Scholar 

  • Achilefu S, Jimenez HN, Dorshow RB et al (2002) Synthesis, in vitro receptor binding, and in vivo evaluation of fluorescein and carbocyanine peptide-based optical contrast agents. J Med Chem 45:2003–2015

    PubMed  CAS  Google Scholar 

  • Akeson M, Sainz E, Mantey SA et al (1997) Identification of four amino acids in the gastrin-releasing peptide receptor that are required for high affinity agonist binding. J Biol Chem 272:17405–17409

    PubMed  CAS  Google Scholar 

  • Aloj L, Morelli G (2004) Design, synthesis and preclinical evaluation of radiolabeled peptides for diagnosis and therapy. Curr Pharm Des 10:3009–3031

    PubMed  CAS  Google Scholar 

  • Alves S, Correia JD, Santos I et al (2006) Pyrazolyl conjugates of bombesin: a new tridentate ligand framework for the stabilization of fac-[M(CO)3] + moiety. Nucl Med Biol 33:625–634

    PubMed  CAS  Google Scholar 

  • Anastasi A, Erspamer V, Bucci M (1971) Isolation and structure of bombesin and alytesin, two analogous active peptides from the skin of the European amphibians Bombina and Alytes. Experientia 27:166–167

    PubMed  CAS  Google Scholar 

  • Anderson CJ, Welch MJ (1999) Radiometal labeled agents (non-technetium) for diagnostic imaging. Chem Rev 99:2219–2234

    PubMed  CAS  Google Scholar 

  • Aprikian AG, Tremblay L, Han K et al (1997) Bombesin stimulates the motility of human prostate-carcinoma cells through tyrosine phosphorylation of focal adhesion kinase and of integrin-associated proteins. Int J Cancer 72:498–504

    PubMed  CAS  Google Scholar 

  • Avis IL, Kovacs TOG, Kasprzyk PG et al (1991) Preclinical evaluation of an anti-autocrine growth factor monoclonal antibody for treatment of patients with small cell lung cancer. J Natl Cancer Inst 83:1470–1476

    PubMed  CAS  Google Scholar 

  • Battey J, Wada E, Corjay M et al (1992) Molecular genetic analysis of two distinct receptors for mammalian bombesin-like peptides. J Natl Cancer Inst Monogr 13:141–144

    PubMed  Google Scholar 

  • Biddlecombe GB, Rogers BE, de Visser M et al (2007) Molecular imaging of gastrin-releasing peptide receptor-positive tumors in mice using 64Cu- and 86Y-DOTA-(Pro 1, Tyr 4)-bombesin(1–14). Bioconjug Chem 18:724–730

    PubMed  CAS  Google Scholar 

  • Blower PJ, Lewis JS, Zweit J (1996) Copper radionuclide and radiopharmaceuticals in nuclear medicine. Nucl Med Biol 23:957–980

    PubMed  CAS  Google Scholar 

  • Brans L, Maes V, Garcia-Garayoa E et al (2008) Glycation methods for bombesin analogs containing the (NalphaHis) Ac chelator for 99mTc(CO)3 radiolabeling. Chem Biol Drug Des 72:496–506

    PubMed  CAS  Google Scholar 

  • Breeman WA, Kwekkeboom DJ, Kooij PP et al (1995) Effect of dose and specific activity on tissue distribution of indium-111-pentetreotide in rats. J Nucl Med 36:623–627

    PubMed  CAS  Google Scholar 

  • Breeman WA, Hofland LJ, de Jong M et al (1999) Evaluation of radiolabeled bombesin analogs for receptortargeted scintigraphy and radiotherapy. Int J Cancer 81:658–665

    PubMed  CAS  Google Scholar 

  • Breeman WA, de Jong M, Erion JL et al (2002) Preclinical comparison of (111)In-labeled DTPA- or DOTA-bombesin analogs for receptor-targeted scintigraphy and radionuclide therapy. J Nucl Med 43:1650–1656

    PubMed  CAS  Google Scholar 

  • Breeman WA, de Jong M, de Blois E et al (2005) Radiolabeling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging 32:478–485

    PubMed  CAS  Google Scholar 

  • Broan CJ, Cox JPL, Craig AS et al (1991) Structure and solution stability of indium and gallium complexes of 1,4,7-triazacyclononatriacetate and yttrium complexes of 1,4,7,10-tetraazacyclododecanetetraacetate and related ligans: kinectically stable complexes for use in imaging and radioimmunotheraphy. X-ray molecular structure of the indium and gallium complexes of 1,4,7-triazacyclononane-1,4,7-triacetic acid. J Chem Soc Perkin Trans 2:87–99

    Google Scholar 

  • Brom M, Joosten L, Laverman P et al (2011) Preclinical evaluation of 68Ga-DOTA-minigastrin for the detection of cholecystokinin-2/gastrin receptor-positive tumors. Mol Imaging 10:144–152

    PubMed  CAS  Google Scholar 

  • Brooks PC, Clark RA, Cheresh DA (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264:569–571

    PubMed  CAS  Google Scholar 

  • Brown M, Tache Y, Fisher D (1979) Central nervous system action of bombesin: mechanism to induce hyperglycemia. Endocrinology 105:660–665

    PubMed  CAS  Google Scholar 

  • Brunner UK, Renn O, Li M et al (1995) In principal of nuclear medicine, Philadelphia, pp 220–229

    Google Scholar 

  • Bunnett N (1994) Gastrin-releasing peptide. In: Walsh JH, Dockray GJ (eds) Gut peptides: biochemistry, and physiology. Raven, New York, pp 423–445

    Google Scholar 

  • Cai RZ, Reile H, Armatis P et al (1994) Potent bombesin antagonists with C terminal Leu-ψ(CH2-N)-Tac-NH2 or its derivatives. Proc Natl Acad Sci USA 91:12664–12668

    PubMed  CAS  Google Scholar 

  • Carlsson J, Forssell-Aronsson E, Hietala SO et al (2003) Tumor theraphy with radionuclides: assessment of progress and problems. Radiother Oncol 66:107–117

    PubMed  CAS  Google Scholar 

  • Cescato R, Maina T, Nock B et al (2008) Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J Nucl Med 49:318–326

    PubMed  CAS  Google Scholar 

  • Chen X, Park R, Hou Y et al (2004) MicroPET and autoradiographic imaging of GRP receptor expression with 64Cu-DOTA-[Lys3]bombesin in human prostate adenocarcinoma xenografts. J Nucl Med 45:1390–1397

    PubMed  CAS  Google Scholar 

  • Chong HS, Garmestani K, Ma D et al (2002) Synthesis and biological evalution of novel macrocyclic ligands with pendent donor groups as potential yttrium chelators for radioimmunotheraphy with improved complex formation kinectics. J Med Chem 45:3458–3464

    PubMed  CAS  Google Scholar 

  • Christiansen J, Holst JJ, Kalaja E (1976) Inhibition of gastric acid in man by exogenous and endogenous pancreatic glucagon. Gastroenterology 70:688–692

    PubMed  CAS  Google Scholar 

  • Clarke ET, Martell AE (1991) Stabilities of the trivalent metal ion complexes of the tetracetate derivatives of 12-, 13-, and 14-membered tetraazamacrocycles. Inorg Chim Acta 190:37–46

    CAS  Google Scholar 

  • Cornelio DB, Roesler R, Schwartsmann G (2007) Gastrin-releasing peptide receptor as a molecular target in experimental anticancer therapy. Ann Oncol 18:1457–1466

    PubMed  CAS  Google Scholar 

  • Craig AS, Parker D, Adams H et al (1989) Stability Ga-71 Nmr and crystal-structure of a Neutral Gallium (iii) complex of 1,4,7-Triazacyclononanetriacetate—a potential radiopharmaceutical. J Chem Soc-Chem Communications, pp 1793–1794

    Google Scholar 

  • Cutler CS, Smith CJ, Ehrhardt GJ et al (2000) Current and potential therapeutic uses of lanthanide radioisotopes. Cancer Biother Radiopharm 15:531–545

    PubMed  CAS  Google Scholar 

  • Cuttitta F, Carney DN, Mulshine J et al (1985) Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316:823–825

    PubMed  CAS  Google Scholar 

  • de Jong M, Bakker WH, Krenning EP et al (1997) Yttrium -90 and indium -111 labeling receptor binding and biodistribution of [DOTA0, d-Phe1, Tyr3]octreotide, a promising somastostatin analog for radionuclide theraphy. Eur J Nucl Med 24:368–371

    PubMed  Google Scholar 

  • de Visser M, Bernard HF, Erion JL et al (2007) Novel (111) In-labeled bombesin analogs analogs for molecular imaging of prostate tumors. Eur J Nucl Med Mol Imaging 34:1228–1238

    PubMed  Google Scholar 

  • Dimitrakopoulou-Strauss A, Hohenberger P, Eisenhut M et al (2006) J Nucl Med 47:102P

    Google Scholar 

  • Dimitrakopoulou-Strauss A, Hohenberger P, Haberkorn U et al (2007) 68Ga-labeled bombesin studies in patients with gastrointestinal stromal tumors: comparisonwith 18F-FDG. J Nucl Med 48:1245–1250

    PubMed  CAS  Google Scholar 

  • Durkan K, Lambrecht FY, Unak P et al (2007) Radiolabeling of bombesin-like peptide with 99 mTc: 99 mTc-litorin and biodistribution in rats. Bioconjug Chem 18:1516–1520

    PubMed  CAS  Google Scholar 

  • Dymov AM, Savostin AP (1968) Analytical chemistry of gallium. Ann Arbor: Ann Arbor Science, Moscow

    Google Scholar 

  • Eary JF (2001) PET imaging for planning cancer theraphy. J Nucl Med 42:770–771

    PubMed  CAS  Google Scholar 

  • Eisenwiener KP, Prata MI, Buschmann I et al (2002) NODAGATOC, a new chelator-coupled somatostatin analog labeled with [67/68Ga] and [111In] for SPECT, PET and targeted therapeutic application of somatostatin receptor (hsst2) expressing tumors. Bioconjug Chem 13:530–541

    PubMed  CAS  Google Scholar 

  • Erspamer V (1988) Discovery, isolation and characterization of bombesin- like peptides. Ann N Y Acad Sci 547:3–9

    PubMed  CAS  Google Scholar 

  • Erspamer V, Erpamer GF, Inselvini M (1970) Some pharmacological actions of alytesin and bombesin. J Pharm Pharmacol 22:875–876

    PubMed  CAS  Google Scholar 

  • Faintuch BL, Teodoro R, Duatti A et al (2008) Radiolabeled bombesin analogs for prostate cancer diagnosis: preclinical studies. Nucl Med Biol 35:401–411

    PubMed  CAS  Google Scholar 

  • Fathi Z, Corjay MH, Shapira H et al (1993) BRS-3: a novel bombesin receptor subtype selectively expressed in testis, and lung carcinoma cells. J Biol Chem 268:5979–5984

    PubMed  CAS  Google Scholar 

  • Ferro-Flores G, Arteaga de Murphy C, Rodriguez-Cortes J et al (2006) Preparation and evaluation of 99 mTc-EDDA/HYNIC-[Lys 3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumors. Nucl Med Commun 27:371–376

    PubMed  CAS  Google Scholar 

  • Fichna J, Janecka A (2003) Synthesis of target-specific radiolabed peptide for diagnostic imaging. Bioconjug Chem 14:3–17

    PubMed  CAS  Google Scholar 

  • Fischer JB, Schonbrunn A (1988) The bombesin receptor is coupled to a guanine nucleotide-binding protein which is insensitive to pertussis and cholera toxins. J Biol Chem 263:2808–2816

    PubMed  CAS  Google Scholar 

  • Forrer F, Valkema R, Kwekkeboom DJ et al (2007) Neuroendocrine tumors. Peptide receptor radionuclide therapy. Best Pract Res Clin Endocrinol Metab 21:111–129

    PubMed  CAS  Google Scholar 

  • Fragogeorgi EA, Zikos C, Gourni E et al (2009) Spacer site modifications for the improvement of the in vitro and in vivo binding properties of (99m)Tc-N(3)S-Xbombesin[2–14] derivatives. Bioconjug Chem 20:856–867

    PubMed  CAS  Google Scholar 

  • Friedlander M, Brooks PC, Shaffer RW et al (1995) Definition of two angiogenic pathways by distinct alpha v integrins. Science 270:1500–1502

    PubMed  CAS  Google Scholar 

  • Gambhir SS (2002) Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2:683–693

    PubMed  CAS  Google Scholar 

  • Garcia GE, Ruegg D, Blauenstein P et al (2007a) Chemical and biological characterization of new Re(CO)3/[99 mTc](CO)3 bombesin analogs. Nucl Med Biol 34:17–28

    Google Scholar 

  • Garcia GE, Schweinsberg C, Maes V et al (2007b) A new [99 mTc] bombesin analogs with improved biodistribution for targeting gastrin releasing-peptide receptorpositive tumors. Q J Nucl Med Mol Imaging 51:42–50

    Google Scholar 

  • Garrison JC, Rold TL, Sieckman GL et al (2007) In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: Side-by-side comparison of the CB-TE2A and DOTA chelation systems. J Nucl Med 48:1327–1337

    PubMed  CAS  Google Scholar 

  • Garrison JC, Rold TL, Sieckman GL et al (2008) Evaluation of the pharmacokinetic effects of various linking group using the 111In-DOTA-X-BBN (7–14)NH2 structural paradigm in a prostate cancer model. Bioconjug Chem 19:1803–1812

    PubMed  CAS  Google Scholar 

  • Ghatei MA, George SK, Major JH et al (1984) Bombesin-like immunoreactivity in the pancreas of man and other mammalian species. Experientia 40:884–886

    PubMed  CAS  Google Scholar 

  • Gibril F, Jensen RT (2004) Diagnostic uses of radiolabeled somatostatin-receptor analogs in gastroenteropancreatic endocrine tumors. Dig Liver Dis 36:S106–S120

    PubMed  CAS  Google Scholar 

  • Giraud AS, Dumesny C, Whitley JC et al (2010) Isolation, identification and biological activity of gastrin-releasing peptide 1–46 (GRP 1–46), the primary GRP gene-derived peptide product of the pregnant ovine endometrium. Peptides 31:284–290

    PubMed  CAS  Google Scholar 

  • Gonzalez N, Moody TW, Igarashi H et al (2008) Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. Curr Opin Endocrinol Diabetes Obes 15:58–64

    PubMed  CAS  Google Scholar 

  • Gonzalez N, Mantey SA, Pradhan TK et al (2009) Characterization of putative GRP- and NMB-receptor antagonist’s interaction with human receptors. Peptides 30:1473–1486

    PubMed  CAS  Google Scholar 

  • Gourni E, Paravatou M, Bouziotis P et al (2006) Evaluation of a series of new 99 mTc-labeled bombesin-like peptides for early cancer detection. Anticancer Res 26:435–438

    PubMed  CAS  Google Scholar 

  • Gourni E, Bouziotis P, Benaki D et al (2009) Structural assessment and biological evaluation of two N3S bombesin derivatives. J Med Chem 52:4234–4246

    PubMed  CAS  Google Scholar 

  • Green MA, Welch MJ (1989) Gallium radiopharmaceutical chemistry. Nucl Med Biol 16:435–448

    CAS  Google Scholar 

  • Gugger M, Reubi JC (1999) Gastrin-releasing peptide receptors in non-neoplastic and neoplastic human breast. Am J Pathol 155:2067–2076

    PubMed  CAS  Google Scholar 

  • Hajri A, Koenig M, Balboni G et al (1996) Expression and characterization of gastrin-releasing peptide receptor in normal and cancerous pancreas. Pancreas 12:25–35

    PubMed  CAS  Google Scholar 

  • Halmos G, Schally AV (1997) Reduction in receptors for bombesin and epidermal growth factor in xenografts of human small-cell lung cancer after treatment with bombesin antagonist RC-3095. Proc Natl Acad Sci USA 94:956–960

    PubMed  CAS  Google Scholar 

  • Harris WR, Messori LA (2002) A comparative study of aluminium(III), gallium(III), indium(III), and thallium(III) binding to human serum tansferrin. Coord Chem Rev 228:237–262

    CAS  Google Scholar 

  • Haubner R, Bruchertseifer F, Bock M et al (2004) Synthesis and biological evalution of a (99m) Tc-labeled Cyclic RGD peptide for imaging the alphabeta3 expression. Nuklearmedizin 43:26–32

    PubMed  CAS  Google Scholar 

  • Heasley LE (2001) Autocrine and paracrine signaling through neuropeptide receptors in human cancer. Oncogene 20:1563–1569

    PubMed  CAS  Google Scholar 

  • Hellmich MR, Ives KL, Udupi V et al (1999) Multiple protein kinase pathways are involved in gastrin-releasing peptide receptor-regulated secretion. J Biol Chem 274:23901–23909

    PubMed  CAS  Google Scholar 

  • Heppeler A, Froidevaux S, Macke HR et al (1999) Radiometal-labeled macrocyclic chelator-derivatised somastostatin analog with superb tumor-targeting properties and potential for receptor mediated internal radiotheraphy. Chem Eur J 5:1974–1981

    CAS  Google Scholar 

  • Heppler A, Froidevaux S, Eberle AN et al (2000) Receptor imaging for tumor localisation and theraphy with radioisopes. Curr Med Chem 7:971–994

    Google Scholar 

  • Hnatowich DJ, Friedman B, Clancy B et al (1981) Labeling of performed liposomes with Ga-67 and Tc-99 m by chelation. J Nucl Med 22:810–814

    PubMed  CAS  Google Scholar 

  • Ho CL, Chen LC, Lee WC et al (2009) 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 24:435–443

    PubMed  CAS  Google Scholar 

  • Hoffman TJ, Gali H, Smith CJ et al (2003) Novel series of 111In-labeled bombesin analogs as potential radiopharmaceuticals for specific targeting of gastrin-releasing peptide receptors expressed on human prostate cancer cells. J Nucl Med 44:823–831

    PubMed  CAS  Google Scholar 

  • Hofmann M, Maecke H, Borner R et al (2001) Biokinectics and imaging with the somatostatin receptor PET radioligand (68) Ga-DOTATOC: preliminary data. Eur J Nucl Med 28:1751–1757

    PubMed  CAS  Google Scholar 

  • Hofmann M, Machtens S, Stief C et al (2004) Feasibility of Ga-68-DOTABOM PET in prostate carcinoma patients [abstract]. J Nucl Med 45:449P

    Google Scholar 

  • Hohne A, Mu L, Honer M et al (2008) Synthesis, 18F-labeling, and in vitro and in vivo studies of bombesin peptides modified with silicon-based building blocks. Bioconjug Chem 19:1871–1879

    PubMed  CAS  Google Scholar 

  • Hu F, Cutler CS, Hoffman T et al (2002) Pm-149 DOTA bombesin nalogs for potential radiotherapy—In vivo comparison with Sm-153 and Lu-177 labeled DO3A-amide-Ala-BBN(7–14)NH2. Nucl Med Biol 29:423–430

    PubMed  CAS  Google Scholar 

  • Jensen RT (1994) Receptors for bombesins. In: Johnson LR (ed) Physiology of the Gastrointestinal Tract. Raven, New York, pp 1387–1393

    Google Scholar 

  • Jensen RT (1997) Peptide therapy. Recent advances in the use of somatostatin and other peptide receptor agonists and antagonists. In: Lewis JH, Dubois A (eds) Current clinical topics in gastrointestinal pharmacology. Blackwell Science, Malden, pp 144–223

    Google Scholar 

  • Jensen RT, Coy DH (1991) Progress in the development of potent bombesin receptor antagonists. Trends Pharmacol Sci 12:13–19

    PubMed  CAS  Google Scholar 

  • Jensen RT, Moody TW (2006) Bombesin-related peptides and neurotensin: effects on cancer growth/proliferation and cellular signaling in cancer. In: Kastin AJ (ed) Handbook of biologically active peptides, 1st edn. Amsterdam, Elsevier, pp 429–434

    Google Scholar 

  • Jensen RT, Battey JF, Spindel ER et al (2008) International Union of Pharmacology. LVIII. Mammalian Bombesin Receptors: Nomenclature, distribution, pharmacology, signalling and functions in normal and disease states. Pharmacol Rev 60:1–42

    PubMed  CAS  Google Scholar 

  • Kane MA, Toi-Scott M, Johnson GL et al (1996) Bombesin-like peptide receptors in human bronchial epithelial cells. Peptides 17:111–118

    PubMed  CAS  Google Scholar 

  • Kiehne K, Herzig KH, Folsch UR (2002) Differential activation of p43ERK2 and p125FAK by cholecystokinin and bombesin in the secretion and proliferation of the pancreatic amphicrine cell line AR42J. Pancreatology 2:46–53

    PubMed  CAS  Google Scholar 

  • Kim HJ, Evers BM, Guo Y et al (1996) Bombesin-mediated AP-1 activation in a human gastric cancer (SIIA). Surgery 120:130–136; discussion 136–137

    Google Scholar 

  • Koh SW, Leyton J, Moody TW (1999) Bombesin activates MAP kinase in non-small cell lung cancer cells. Peptides 20:121–126

    PubMed  CAS  Google Scholar 

  • Koizumi M, Endo K, Kunimatsu M et al (1987) Preparation of 67 Ga-labeled antibodies using deferoxamine as a bifunctional chelate an improved method. J Immunological Methods 104:93–102

    CAS  Google Scholar 

  • Koumarianou E, Mikolajczak R, Pawlak D et al (2009) Comparative study on DOTA-derivatized bombesin analog labeled with 90Y and 177Lu: in vitro and in vivo evaluation. Nucl Med Biol 36:591–603

    PubMed  CAS  Google Scholar 

  • Kowalski J, Henze M, Schumacher J et al (2003) Evalution of positron emission tomography imaging using [68Ga]-DOTA-D-Phe(1)-Tyr(3)-Octreotide in comparison to [111In]-DTPAOC SPECT. First resuls in patients with neuroendocrine tumor. Mol Imaging Biol 5:42–48

    PubMed  Google Scholar 

  • Krenning EP, Kwekkeboom DJ, Bakker WH et al (1993) Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1,000 patients. Eur J Nucl Med 20:716–731

    PubMed  CAS  Google Scholar 

  • Krenning EP, Kwekkeboom DJ, Valkema R et al (2004) Peptide receptor radionuclide therapy. Ann N Y Acad Sci 1014:234–245

    PubMed  CAS  Google Scholar 

  • Kroog GS, Jensen RT, Battey JF (1995) Mammalian bombesin receptors. Med Res Rev 15:389–417

    PubMed  CAS  Google Scholar 

  • Kung MP, Kung HF (2005) Mass effect of injected dose in small rodent imaging by SPECT and PET. Nucl Med Biol 32:673–678

    PubMed  CAS  Google Scholar 

  • Kunstler JU, Veerendra B, Figueroa SD et al (2007) Organometallic 99mTc(III) ‘4 + 1’ bombesin(7–14) conjugates: synthesis, radiolabeling, and in vitro/in vivo studies. Bioconjug Chem 18:1651–1661

    PubMed  CAS  Google Scholar 

  • Kwekkeboom D, Krenning EP, de Jong M (2000) Peptide receptor imaging and therapy. J Nucl Med 41:1704–1713

    PubMed  CAS  Google Scholar 

  • La Bella R, Garcia-Garayoa E, Langer M et al (2002) In vitro and in vivo evaluation of a 99 mTc(I)-labeled bombesin analog for imaging of gastrin releasing peptide receptor-positive tumors. Nucl Med Biol 29:553–560

    PubMed  Google Scholar 

  • Ladenheim EE, Taylor JE, Coy DH et al (1994) Blockade of feeding inhibition by neuromedin B using a selective receptor antagonist. Eur J Pharmacol 271:R7–R9

    PubMed  CAS  Google Scholar 

  • Lambrecht RM, Sajjad M (1988) Accelarator-derived radionuclide generators. Radiochim Acta 43:171–179

    CAS  Google Scholar 

  • Lane SR, Veerendra B, Rold TL et al (2008) 99mTc(CO)3-DTMA bombesin conjugates having high affinity for the GRP receptor. Nucl Med Biol 35:263–272

    PubMed  CAS  Google Scholar 

  • Lantry LE, Cappelletti E, Maddalena ME et al (2006) 177Lu-AMBA: Synthesis and characterization of a selective 177Lu-labeled GRP-R agonist for systemic radiotherapy of prostate cancer. J Nucl Med 47:1144–1152

    PubMed  CAS  Google Scholar 

  • Laskin JJ, Sandler AB (2004) Epidermal growth factor receptor: a promising target insolid tumors. Cancer Treat Rev 30:1–17

    PubMed  CAS  Google Scholar 

  • Lebacq-Verheyden AM, Trepel J, Sausville EA et al (1990) Bombesin and gastrin-releasing peptide: neuropeptides, secretagogues, and growth factors. In: Sporn MB, Roberts AB (eds) Peptide growth factors and their receptors II. Springer, New York, pp 71–124

    Google Scholar 

  • Lewis MR, Raubitschek A, Shively JE (1994) A facile, water soluble method for modification of proteins with DOTA. Use of elevated temperature and optimized pH to achieve high specific activity and high chelate stability in radiolabeled immunoconjugates. Bioconjug Chem 5:565–576

    PubMed  CAS  Google Scholar 

  • Li WP, Lewis JS, Kim J et al (2002) DOTA-D-Tyr1-octreotate: a somatostatin analog for labeling with metal and halogen radionuclides for cancer imaging and therapy. Bioconjug Chem 13:721–728

    PubMed  CAS  Google Scholar 

  • Li ZB, Wu Z, Chen K et al (2008) 18F-labeled BBN-RGD heterodimer for prostate cancer imaging. J Nucl Med 49:453–461

    PubMed  CAS  Google Scholar 

  • Liehr RM, Reidelberger RD, Rosewicz S et al (1992) Dose-related involvement of CCK in bombesin-induced pancreatic growth. Regul Pept 38:207–219

    PubMed  CAS  Google Scholar 

  • Lin TM, Warrick MW (1974) Action of acetylsalicyclic acid and glucagon on aicd secretion mucosal blood flow, bleeding, and net ionic effux in the fundic pouch of pentagastrin stimulated dogs. Arch Int Pharmacol Ther 210:279–287

    CAS  Google Scholar 

  • Lin KS, Luu A, Baidoo KE et al (2005) A new high affinity technetium-99 m-bombesin analog with low abdominal accumulation. Bioconjug Chem 16:43–50

    PubMed  CAS  Google Scholar 

  • Liu S, Edwards DS (2001a) Synthesis and characterization of two (111)-In-labeled DTPA-peptide conjugates. Bioconjug Chem 12:630–634

    PubMed  CAS  Google Scholar 

  • Liu S, Edwards DS (2001b) Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconjug Chem 12:7–34

    PubMed  Google Scholar 

  • Liu Z, Niu G, Wang F et al (2009a) (68)Ga-labeled NOTARGD- BBN peptide for dual integrin and GRPR-targeted tumor imaging. Eur J Nucl Med Mol Imaging 36:1483–1494

    PubMed  CAS  Google Scholar 

  • Liu Z, Yan Y, Chin FT et al (2009b) Dual integrin and gastrin releasing peptide receptor targeted tumor imaging using 18F-labeled PEGylated RGD-bombesin heterodimer 18F-FBPEG3- Glu-RGD-BBN. J Med Chem 52:425–432

    PubMed  CAS  Google Scholar 

  • Liu Z, Li ZB, Cao Q et al (2009c) Small animal PET of tumors with (64)Cu-labeled RGD-bombesin heterodimer. J Nucl Med 50:1168–1177

    PubMed  CAS  Google Scholar 

  • Llinares M, Devin C, Chaloin O et al (1999) Syntheses and biological activities of potent bombesin receptor antagonists. J Pept Res 53:275–283

    PubMed  CAS  Google Scholar 

  • Lundqvist H, Tolmchev V (2002) Targeting peptides and positron emission tomography. Bioploymers 66:381–392

    CAS  Google Scholar 

  • Luyt LG, Katzenellenbogen JA (2002) A trithiolate tripodal bifunctional ligan for the radiolabeling of peptides with gallium (III). Bioconjug Chem 13:1140–1145

    PubMed  CAS  Google Scholar 

  • Ma L, Yu P, Veerendra B et al (2007) 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 6:171–180

    PubMed  CAS  Google Scholar 

  • Maecke HR, Hofmann M, Haberkorn U (2005) 68Ga-labeled peptide in tumor imaging. J Nucl Med 46:172S–178S

    PubMed  CAS  Google Scholar 

  • Maes V, Brans L, Schweinsberg C et al (2009) Carbohydrated [99mTc(CO)3](NalphaHis)Ac-bombesin(7–14) analogs. Adv Exp Med Biol 611:409–410

    PubMed  CAS  Google Scholar 

  • Maina T, Nock B, Mather S (2006) Targeting prostate cancer with radiolabeled bombesins. Cancer Imaging 6:153–157

    PubMed  Google Scholar 

  • Mansi R, Wang X, Forrer F et al (2009) Evaluation of a therapeutic radionuclides tomography, positron emission tomography, and labeling with single-photon emission computed conjugated bombesin-based radioantagonist for the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Clin Cancer Res 15:5240–5249

    PubMed  CAS  Google Scholar 

  • Mantey SA, Weber HC, Sainz E et al (1997) Discovery of a high affinity radioligand for the human orphan receptor, bombesin receptor subtype 3, which demonstrates that it has a unique pharmacology compared with other mammalian bombesin receptors. J Biol Chem 272:26062–26071

    PubMed  CAS  Google Scholar 

  • Markwalder R, Reubi JC (1999) Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res 59:1152–1159

    PubMed  CAS  Google Scholar 

  • Mathias CJ, Sun YZ, Welch MJ et al (1990) N,N’-bis(2-hydroxybenzyl)-1-(4-bromoacetamidobenzyl)-1,2-ethylenediamine-N,N’-diacetic acid: a new bifunctional chelates for radiolabeling antibodies. Bioconjug Chem 1:204–211

    PubMed  CAS  Google Scholar 

  • Matsumoto K, Yamada K, Wada E et al (2003) Bombesin receptor subtype-3 modulates plasma insulin concentration. Peptides 24:83–90

    PubMed  CAS  Google Scholar 

  • McDevitt MR, Ma D, Lai LT et al (2001) Tumor theraphy with targeted atomic nanogenerators. Science 294:1537–1540

    PubMed  CAS  Google Scholar 

  • McDonald TJ, Jornvall H, Nilsson G et al (1979) Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue. Biochem Biophys Res Commun 90:227–233

    PubMed  CAS  Google Scholar 

  • Metz DC, Jensen RT (2008) Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 135:1469–1492

    PubMed  CAS  Google Scholar 

  • Meyer GJ, Gielow P, Borner AR et al (2005) Ga-67 and Ga-68 labeled DOTA-derivatised peptide-ligands. Nuklearmedizin 6:A192

    Google Scholar 

  • Minamino N, Kangawa K, Matsuo H (1983) Neuromedin B: a novel bombesin-like peptide identified in porcine spinal cord. Biochem Biophys Res Commun 114:541–548

    PubMed  CAS  Google Scholar 

  • Minamino N, Kangawa K, Matsuo H (1984) Neuromedin C: a bombesinlike peptide identified in porcine spinal cord. Biochem Biophys Res Commun 119:14–20

    PubMed  CAS  Google Scholar 

  • Mollet A, Meier S, Grabler V et al (2003) Endogenous amylin contributes to the anorectic effects of cholecystokinin and bombesin. Peptides 24:91–98

    PubMed  CAS  Google Scholar 

  • Montet X, Weissleder R, Josephson L (2006) Imaging pancreatic cancer with a peptide nanoparticle conjugate targeted to normal pancreas. Bioconjug Chem 17:905–911

    PubMed  CAS  Google Scholar 

  • Moody TW, Crawley JN, Jensen RT (1982) Pharmacology and neurochemistry of bombesin-like peptides. Peptides 3:559–563

    PubMed  CAS  Google Scholar 

  • Moody TW, Chan D, Fahrenkrug J et al (2003) Neuropeptides as autocrine growth factors in cancer cells. Curr Pharm Des 9:495–509

    PubMed  CAS  Google Scholar 

  • Moody TW, Mantey SA, Pradhan TK et al (2004) Development of high affinity camptothecin-bombesin conjugates that have targeted cytotoxicity for bombesin receptor containing tumor cells. J Biol Chem 279:23580–23589

    PubMed  CAS  Google Scholar 

  • Moore JG (1973) Gastric acid suppression by inravenous glucose solutions. Gastroenterology 64:1106–1110

    PubMed  CAS  Google Scholar 

  • Moran TH, Moody W, Hostetler AM et al (1988) Distribution of bombesin binding sites in the rat gastrointestinal tract. Peptides 9:643–649

    PubMed  CAS  Google Scholar 

  • Mutic S, Malyapa RS, Grigsby PW et al (2003) PET-guided IMRT for cervical carcinoma with positive para-aortic lymph nodes-a-dose-escaltion treatment planning study. Int J Radiat Oncol Biol Phys 55:28–35

    PubMed  Google Scholar 

  • Nagalla SR, Gibson BW, Tang D et al (1992) Gastrinreleasing peptide (GRP) is not mammalian bombesin. Identification and molecular cloning of a true amphibian GRP distinct from amphibian bombesin in Bombina orientalis. J Biol Chem 267:6916–6922

    PubMed  CAS  Google Scholar 

  • Nanda PK, Lane SR, Retzloff LB et al (2010) Radiolabeled regulatory peptides for imaging and therapy. Curr Opin Endocrinol Diabetes Obes 17:69–76

    PubMed  CAS  Google Scholar 

  • Narayan S, Guo YS, Townsend CM et al (1990) Specific binding and growth effects of bombesin-related peptides on mouse colon cancer cells in vito. Cancer Res 50:6772–6778

    PubMed  CAS  Google Scholar 

  • Nemeroff CB, Osbahr AJ, Manberg PJ et al (1979) Alteration in nociception and body temperature after intracisternal administration of neurotensin, β-endorphin, other endogenous peptides, and morohine. Proc Natl Acad Sci USA 76:5368–5371

    PubMed  CAS  Google Scholar 

  • Nock B, Nikolopoulou A, Chiotellis E et al (2003) A novel potent bombesin analog for GRP receptor-targeted tumor imaging. Eur J Nucl Med Mol Imaging 30:247–258

    PubMed  CAS  Google Scholar 

  • Nock BA, Nikolopoulou A, Galanis A et al (2005) Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. J Med Chem 48:100–110

    PubMed  CAS  Google Scholar 

  • Okarvi SM (1999) Recent developments in 99mTc-labeled peptide-based radiopharmaceuticals: an overview. Nucl Med Commun 20:1093–1112

    PubMed  CAS  Google Scholar 

  • Okarvi SM (2004) Peptide-based radiopharmaceuticals: future tools for diagnostic imaging of cancers and other diseases. Med Res Rev 24:357–397

    PubMed  CAS  Google Scholar 

  • Okarvi SM (2008) Peptide-based radiopharmaceuticals and cytotoxic conjugates: potential tools against cancer. Cancer Treat Rev 34:13–26

    PubMed  CAS  Google Scholar 

  • Okarvi SM, Al-Jammaz I (2003) Synthesis, radiolabeling and biological characteristics of a bombesin peptide analog as a tumor imaging agent. Anticancer Res 23:2745–2750

    PubMed  CAS  Google Scholar 

  • Osumi Y, Aibara S, Sakae K et al (1977) Central noradrenergic inhibition of gastric mucosal blood flow and acid secretion in rats. Life Sci 20:1407–1416

    PubMed  CAS  Google Scholar 

  • Parry JJ, Andrews R, Rogers BE (2007) MicroPET imaging of breast cancer using radiolabeled bombesin analogs targeting the gastrin-releasing peptide receptor. Breast Cancer Res Treat 101:175–183

    PubMed  CAS  Google Scholar 

  • Paterson BM, Karas JA, Scanlon DB et al (2010) Synthesis, conjugation to bombesin (7–14)-NH2, and copper-64 radiolabeling. Inorg Chem 49:1884–1893

    PubMed  CAS  Google Scholar 

  • Pazos-Moura CC, Ortiga-Carvalho TM, Gaspar De Moura E (2003) The autocrine/paracrine regulation of thyrotropin secretion. Thyroid 13:167–175

    PubMed  CAS  Google Scholar 

  • Pearson RG (1963) Hard and soft acids and bases. J Am Chem Soc 85:3533–3539

    CAS  Google Scholar 

  • Pochon S, Buchegger F, Pelegrin A et al (1989) A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies. Int J Cancer 43:1188–1194

    PubMed  CAS  Google Scholar 

  • Pradhan TK, Katsuno T, Taylor JE et al (1998) Identification of a unique ligand which has high affinity for all four bombesin receptor subtypes. Eur J Pharmacol 343:275–287

    PubMed  CAS  Google Scholar 

  • Prasanphanich AF, Nanda PK, Rold TL et al (2007) [64Cu-NOTA-8-Aoc-BBN(7–14)NH2] targeting vector for positron-emission tomography imaging of gastrin-releasing peptide receptor-expressing tissues. Proc Natl Acad Sci USA 104:12462–12467

    PubMed  CAS  Google Scholar 

  • Preston SR, Miller GV, Primrose JN (1996) Bombesin-like peptides and cancer. Crit Rev Oncol Hematol 23:225–238

    PubMed  CAS  Google Scholar 

  • Reichert DE, Lewis JS, Andreson CJ (1999) Metal complexes as diagnostic tools. Coord Chem Rev 184:3–66

    CAS  Google Scholar 

  • Retzloff LB, Heinzke L, Figureoa SD et al (2010) Evaluation of [99mTc-(CO)3-X-Y-bombesin(7–14)NH2] conjugates for targeting gastrin-releasing peptide receptors overexpressed on breast carcinoma. Anticancer Res 30:19–30

    PubMed  CAS  Google Scholar 

  • Reubi JC (1995) Neuropeptide receptors in health and disease: the molecular basis for in vivo imaging. J Nucl Med 36:1825–1835

    PubMed  CAS  Google Scholar 

  • Reubi JC (2003) Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 24:389–427

    PubMed  CAS  Google Scholar 

  • Reubi JC, Maecke HR (2008) Peptide-based probes for cancer imaging. J Nucl Med 49:1735–1738

    PubMed  CAS  Google Scholar 

  • Reubi JC, Wenger S, Schmuckli-Maurer J et al (2002) Bombesin receptor subtypes in human cancers: detection with the universal radioligand P 125PI-[DTy6, beta-AlaP11P, PheP 13 P, NleP14] bombesin(6–14). Clin Cancer Res 8:1139–1146

    PubMed  CAS  Google Scholar 

  • Reubi JC, Macke HR, Krenning EP (2005) Candidtae for peptide receptor radiotheraphy today and in the future. J Nucl Med 46:67S–75S

    PubMed  CAS  Google Scholar 

  • Rogers BE, Rosenfeld ME, Khazaeli MB et al (1997) Localization of iodine-125-mIP-Des-Met14-bombesin (7–13)NH2 in ovarian carcinoma induced to express the gastrin releasing peptide receptor by adenoviral vector-mediated gene transfer. J Nucl Med 38:1221–1229

    PubMed  CAS  Google Scholar 

  • Rogers BE, Manna DD, Safavy A (2004) In vitro and in vivo evaluation of a 64Cu-labeled polyethylene glycol-bombesin conjugate. Cancer Biother Radiopharm 19:25–34

    PubMed  CAS  Google Scholar 

  • Rozengurt E (1990) Bombesin stimulation of mitogenesis. Specific receptors, signal transduction and early events. Am Rev Respir Dis 142:S11–S15

    PubMed  CAS  Google Scholar 

  • Rozengurt E (1991) Neuropeptides as cellular growth factors: role of multiple signalling pathways. Eur J Clin Invest 21:123–134

    PubMed  CAS  Google Scholar 

  • Ryan RR, Weber HC, Hou W et al (1998) Ability of various bombesin receptor agonists and antagonists to alter intracellular signaling of the human orphan receptor BRS-3. J Biol Chem 273:13613–13624

    PubMed  CAS  Google Scholar 

  • Sancho V, Di Florio A, Terry W et al (2011) Bombesin receptor-mediated imaging and cytotoxicity: review and current status. Curr Drug Delivery 8:79–134

    CAS  Google Scholar 

  • Santos-Cuevas CL, Ferro-Flores G, Arteaga de Murphy C et al (2008) Targeted imaging of gastrin-releasing peptide receptors with 99mTc-EDDA/HYNIC-[Lys3]-bombesin: biokinetics and dosimetry in women. Nucl Med Commun 29:741–747

    PubMed  CAS  Google Scholar 

  • Santos-Cuevas CL, Ferro-Flores G, Arteaga de Murphy C et al (2009) Design, preparation, in vitro and in vivo evaluation of (99m)Tc-N2S2-Tat(49–57)-bombesin: a target-specific hybrid radiopharmaceutical. Int J Pharm 375:75–83

    PubMed  CAS  Google Scholar 

  • Schroeder RP, Muller C, Reneman S et al (2010) A standardized study to compare prostate cancer targeting efficacy of five radiolabeled bombesin analogs. Eur J Nucl Med Mol Imaging 37:1386–1396

    PubMed  CAS  Google Scholar 

  • Schroeder RPJ, van Weerden WM, Krenning EP et al (2011) Gastrin-releasing peptide receptor-based targeting using bombesin analogs is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts. Eur J Nucl Med Mol Imaging 38:1257–1266

    PubMed  CAS  Google Scholar 

  • Schuhmacher J, Zhang H, Doll J et al (2005) GRP receptor-targeted PET of a rat pancreas carcinoma xenograft in nude mice with a 68Ga-labeled bombesin(6–14) analog. J Nucl Med 46:691–699

    PubMed  CAS  Google Scholar 

  • Schuhmaker J, Atys R, Hauser H et al (1986) Labeling of monoclonal antibodies with a 67 Ga phenolic aminocarboxylic acid chelate. Part I. Chemistry and labeling technique. Eur J Nucl Med 12:397–404

    Google Scholar 

  • Schweinsberg C, Maes V, Brans L et al (2008) Novel glycated [99mTc(CO)3]-labeled bombesin analogs for improved targeting of gastrin-releasing peptide receptor-positive tumors. Bioconjug Chem 19:2432–2439

    PubMed  CAS  Google Scholar 

  • Scopinaro F, Varvarigou AD, Ussof W et al (2002) Technetium labeled bombesin-like peptide: preliminary report on breast cancer uptake in patients. Cancer Biother Radiopharm 17:327–335

    PubMed  CAS  Google Scholar 

  • Scopinaro F, De Vincentis G, Corazziari E et al (2004) Detection of colon cancer with 99mTc-labeled bombesin derivative (99mTc-leu13-BN1). Cancer Biother Radiopharm 19:245–252

    PubMed  CAS  Google Scholar 

  • Scopinaro F, Massari R, Varvarigou AD et al (2007) High resolution small animal single photon emission computed tomography: uptake of [99mTc]bombesin and [123I]ioflupane by rat brain. Q J Nucl Med Mol Imaging 51:204–210

    PubMed  CAS  Google Scholar 

  • Severi C, Coy DH, Jensen RT et al (1989) Pharmacological characterization of [13 Leu13ψ-CH2NH-Leu14]-bombesin as a specific bombesin receptor antagonist on isolated smooth muscle cells. J Pharmacol Exp Ther 251:713–717

    PubMed  CAS  Google Scholar 

  • Seybold VS, Parsons AM, Aanonsen LM et al (1990) Characterization and autoradiographic localization of gastrin releasing peptide receptors in the porcine gut. Peptides 11:779–787

    PubMed  CAS  Google Scholar 

  • Shipp MA, Tarr GE, Chen CY et al (1991) CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung. Proc Natl Acad Sci USA 88:10662–10666

    PubMed  CAS  Google Scholar 

  • Signore A, Annovazzi A, Chianelli M et al (2001) Peptide radiopharmaceuticals for diagnosis and therapy. Eur J Nucl Med 28:1555–1565

    PubMed  CAS  Google Scholar 

  • Smith CJ, Gali H, Sieckman GL et al (2003a) Radiochemical investigations of 177Lu-DOTA-8-Aoc-BBN7- 14NH2: An in vitro/in vivo assessment of the targeting ability of this new radiopharmaceutical for PC-3 human prostate cancer cells. Nucl Med Biol 30:101–109

    PubMed  CAS  Google Scholar 

  • Smith CJ, Gali H, Sieckman GL et al (2003b) Radiochemical investigations of 99 mTc-N3S-X-BBN7-14NH2: An in vitro/in vivo structure-activity relationship study where X) 0-,3-,5-,8-, and 11-carbon tethering moieties. Bioconjug Chem 14:93–102

    PubMed  CAS  Google Scholar 

  • Smith CJ, Sieckman GL, Owen NK et al (2003c) T. J. Radio-Chemical investigations of gastrin-releasing peptide receptorspecific [(99m)Tc(X)(CO)3-Dpr-Ser-Ser–Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH2)] in PC-3, tumor-bearing, rodent models: syntheses, radiolabeling, and in vitro/in vivo studies where Dpr = 2,3-diaminopropionic acid and X = H2O or P(CH2OH)3. Cancer Res 63:4082–4088

    PubMed  CAS  Google Scholar 

  • Smith CJ, Sieckman GL, Owen NK et al (2003d) Radiochemical investigation of [188Re(H2O)(CO)3-diaminoproprionic acid-SSS-bombesin(7–14)NH2]: synthesis, radiolabeling and in vitro/in vivo GRP receptor targeting studies. Anticancer Res 23:63–70

    PubMed  CAS  Google Scholar 

  • Smith CJ, Volkert WA, Hoffman TJ (2003e) Gastrin releasing peptide (GRP) receptor targeted radiopharmaceuticals: a concise update. Nucl Med Biol 30:861–868

    PubMed  CAS  Google Scholar 

  • Smith CJ, Volkert WA, Hoffman TJ (2005) Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes. Nucl Med Biol 32:733–740

    PubMed  CAS  Google Scholar 

  • Spindel E (1986) Mammalian bombesin-like peptides. Trends Neurosci 9:130–133

    CAS  Google Scholar 

  • Stimmel JB, Stockstill ME, Kull FC et al (1995) Yttrium-90 chelation properties of tetrazatetraacetic acid macrocycles, diethylenetriaminepentaacetic acid analogs, and a novel terpyridine acyclic chelator. Bioconjug Chem 6:219–225

    PubMed  CAS  Google Scholar 

  • Sunday ME, Kaplan LM, Motoyama E et al (1988) Gastrin-releasing peptide (mammalian bombesin) gene expression in health and disease. Lab Invest 59:5–24

    PubMed  CAS  Google Scholar 

  • Swope SL, Schonbrunn A (1988) The biphasic stimulation of insulin secretion by bombesin involves both cytosolic free calcium and protein kinase C. Biochem J 253:193–201

    PubMed  CAS  Google Scholar 

  • Tachf Y, Vale W, Rivier J et al (1980) Brain regulation of gastric secretion: influence of neuropeptides (bombesin/8-endorphin/central nervous system/gastric acid output). Proc Natl Acad Sci USA 77:5515–5519

    Google Scholar 

  • Thomas R, Chen J, Roudier MM et al (2009) Vessella RL, Lantry LE, Nunn AD. In vitro binding evaluation of 177Lu-AMBA, a novel 177Lu-labeled GRP-R agonist for systemic radiotherapy in human tissues. Clin Exp Metastasis 26:105–119

    PubMed  CAS  Google Scholar 

  • Tofilon PJ, Saxman S, Coleman CN (2003) Molecular targets for radion theraphy: bringing preclinical data into clinical trials. Clin Cancer Res 9:3518–3520

    PubMed  CAS  Google Scholar 

  • Tweedle MF (2009) Peptide-targeted diagnostics and radiotherapeutics. Acc Chem Res 42:958–968

    PubMed  CAS  Google Scholar 

  • Upp JR, Poston GJ, Maclellan DG et al (1988) Mechanisms of the trophic actions of bombesin on the pancreas. Pancreas 3:193–198

    PubMed  CAS  Google Scholar 

  • Uppal JK, Hazari PP, Varshney R et al (2011) Design, synthesis and biological evaluation of choline based SPECT imaging agent: Ga(III)-DO3A-EA-choline. Org Bio Chem 9(1591):1599

    Google Scholar 

  • Van de Wiele C, Dumont F, Vanden Broecke R et al (2000) Technetium-99 m RP527, a GRP analog for visualisation of GRP receptor-expressing malignancies: a feasibility study. Eur J Nucl Med 27:1694–1699

    PubMed  Google Scholar 

  • Van de Wiele C, Dumont F, Van Belle S et al (2001) Is there a role for agonist gastrin-releasing peptide-receptor radioligands in tumor imaging? Nucl Med Commun 22:5–15

    PubMed  Google Scholar 

  • Van de Wiele C, Phonteyne P, Pauwels P et al (2008) Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry. J Nucl Med 49:260–264

    PubMed  Google Scholar 

  • van de WC, Dumont F, Dierck RA et al (2001) Biodistribution and dosimetry of (99 m)Tc-RP527, a gastrin-releasing peptide (GRP) agonist for the visualization of GRP receptor-expressing malignancies. J Nucl Med 42:1722–1727

    Google Scholar 

  • Van Essen M, Krenning EP, Kam BL et al (2009) Peptide-receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol 5:382–393

    PubMed  Google Scholar 

  • Van Lommel A (2001) Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development. Paediatr Respir Rev 2:171–176

    PubMed  Google Scholar 

  • Varshney R, Hazari PP, Uppal JK et al (2011) Solid phase synthesis, radiolabeling and biological evaluation of a 99mTc-labeled αVβ3 tripeptide (RGD) conjugated to DOTA as a tumor imaging agent. Cancer Bio Therapy 11:1–9

    Google Scholar 

  • Varvarigou AD, Scopinaro F, Leondiadis L et al (2002) Synthesis, chemical, radio-chemical and radiobiological evaluation of a new 99 mTc-labeled bombesin-like peptide. Cancer Biother Radiopharm 17:317–326

    PubMed  CAS  Google Scholar 

  • Varvarigou A, Bouziotis P, Zikos C et al (2004) Gastrin-releasing peptide (GRP) analog for cancer imaging. Cancer Biother Radiopharm 19:219–229

    PubMed  CAS  Google Scholar 

  • Velikyan I (2005) Syntesis, characterization and application of 68Ga-labeled macromolecules. Digital comprehensive summaries of Uppsala dissertations from the Faculty of Science and Technology 73:1651–6214

    Google Scholar 

  • Velikyan I, Sundberg AL, Lindhe O et al (2005) Preparation and evaluation of 68Ga-DOTA-hEGF for visualization of EGFR expression in malignant tumors. J Nucl Med 46:1881–1888

    PubMed  CAS  Google Scholar 

  • Vigna SR, Giraud AS, Mantyh PS et al (1990) Characterization of bombesin receptors on canine antral gastrin cells. Peptides 11:259–264

    PubMed  CAS  Google Scholar 

  • Volkert WA, Hoffman TJ (1999) Therapeutic radiopharmaceuticals. Chem Rev 99:2269–2292

    PubMed  CAS  Google Scholar 

  • Von Schrenck T, Heinz-Erian P, Moran T et al (1989) Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors. Am J Physiol 256:747–758

    Google Scholar 

  • Wagner SJ, Welch MJ (1979) Gallium-68 labeling of albumin and albumin microspheres. J Nucl Med 20:428–433

    PubMed  CAS  Google Scholar 

  • Waser B, Eltschinger V, Linder K et al (2007) Selective in vitro targeting of GRP and NMB receptors in human tumors with the new bombesin tracer 177Lu-AMBA. Eur J Nucl Med Mol Imaging 34:95–100

    PubMed  CAS  Google Scholar 

  • Weiner RE, Thakur ML (2002) Radiolabeled peptides in the diagnosis and therapy of oncological diseases. Appl Radiat Isot 57:749–763

    PubMed  CAS  Google Scholar 

  • Whitley JC, Moore C, Giraud AS et al (1999) Molecular cloning, genomic organization and selective expression of bombesin receptor subtype 3 in the sheep hypothalamus and pituitary. J Mol Endocrinol 23:107–116

    PubMed  CAS  Google Scholar 

  • Wild D, Macke HR, Waser B et al (2005) 68Ga-DOTANOC: a first compound for PET imaging with high affinity for somatostain receptor subtype 2 and 5. Eur J Nucl Med Mol Imaging 32:724

    PubMed  Google Scholar 

  • Yamaguchi I, Hiroi J, Kumada S (1977) Central and peripheral adrenergic mechanisms regulating gastric secretion in the rat. J Pharmacol Exp Ther 203:125–131

    PubMed  CAS  Google Scholar 

  • Yang YS, Zhang X, Xiong Z et al (2006) Comparative in vitro and in vivo evaluation of two 64Cu labeled bombesin analogs in a mouse model of human prostate adenocarcinoma. Nucl Med Biol 33:371–380

    PubMed  CAS  Google Scholar 

  • Yegen BC (2003) Bombesin-like peptides: candidates as diagnostic and therapeutic tools. Curr Pharm Des 9:1013–1022

    PubMed  CAS  Google Scholar 

  • Yoo J, Reichert DE, Welch MJ (2004) Comparative in vivo behaviour studies of cycle bases copper -64 complexes:regioselective synthesis, X-ray structure, radiochemistry, log P and biodistribution. J Med Chem 47:6625–6637

    PubMed  CAS  Google Scholar 

  • Zhang H, Chen J, Waldherr C et al (2004) Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors. Cancer Res 64:6707–6715

    PubMed  CAS  Google Scholar 

  • Zhang X, Cai W, Cao F et al (2006) 18F-labeled bombesin analogs for targeting GRP receptor-expressing prostate cancer. J Nucl Med 47:492–501

    PubMed  CAS  Google Scholar 

  • Zhang HW, Schuhmacher J, Waser B et al (2007) DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumors. Eur J Nucl Med Mol Imaging 34:1198–1208

    PubMed  Google Scholar 

  • Zhou J, Chen J, Mokotoff M et al (2004) Targeting gastrinreleasing peptide receptors for cancer treatment. Anticancer Drugs 15:921–927

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. DCRS, INMAS, DRDO, Brig. S.K. Mazumdar Road, Delhi, 110054, India

    Raunak Varshney, Puja P. Hazari & Anil K. Mishra

  2. University of Bordeaux, CNRS, INCIA, UMR 5287, F-33400 , Talence, France

    P. Fernandez, J. Schulz & M. Allard

Authors
  1. Raunak Varshney
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  2. Puja P. Hazari
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  3. P. Fernandez
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  4. J. Schulz
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  5. M. Allard
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  6. Anil K. Mishra
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Corresponding author

Correspondence to Anil K. Mishra .

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Editors and Affiliations

  1. , THERANOSTICS Center for Molecular,, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, 99437, Germany

    Richard P. Baum

  2. Inst. Kernchemie, Universität Mainz, Fritz-Straßmann-Weg 2, Mainz, 55128, Germany

    Frank Rösch

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Varshney, R., Hazari, P.P., Fernandez, P., Schulz, J., Allard, M., Mishra, A. . (2013). 68Ga-Labeled Bombesin Analogs for Receptor-Mediated Imaging. In: Baum, R., Rösch, F. (eds) Theranostics, Gallium-68, and Other Radionuclides. Recent Results in Cancer Research, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27994-2_12

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  • DOI: https://doi.org/10.1007/978-3-642-27994-2_12

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  • Online ISBN: 978-3-642-27994-2

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