Skip to main content
SpringerLink
Log in

Evaluation of new 99mTc-labeled HYNIC-bombesin analogue for prostate cancer imaging

  • Published:
Journal of Radioanalytical and Nuclear Chemistry Aims and scope Submit manuscript

Abstract

In this study, we introduce a new 99mTc-radiolabeled bombesin derivative for imaging of prostate cancer (PC). We used 6-hydrazinonicotinamide (HYNIC) as bi-functional chelating agent and tricine/ethylenediamine diacetic acid (EDDA) as an exchange co-ligands. Radiolabeling was achieved with high purity and was accompanied with high solution and serum stability. Cellular binding study demonstrated specific binding and internalization of radioconjugate in cultured PC3 cells. In vivo experiments showed fast blood clearance with kidney excretion. Blocking experiments showed decreased uptake of radiopeptide in tumor and pancreas. The results of the imaging using planar SPECT also confirmed suitable tumour uptake for PC3 xenograft nude mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Applegate CC, Rowles JL, Ranard KM, Jeon S, Erdman JW (2017) Soy consumption and the risk of prostate cancer in men: an updated systematic review and meta-analysis. FASEB J 31(1 Supplement):735–790

    Google Scholar 

  2. Brunner C, Davies NM, Martin RM, Eeles R, Easton D, Kote-Jarai Z, Olama A, Amin A, Benlloch S, Muir K (2017) Alcohol consumption and prostate cancer incidence and progression: a Mendelian randomisation study. Int J Cancer 140(1):75–85

    Article  CAS  Google Scholar 

  3. Schroeder RPJ, Van Weerden WM, Bangma C, Krenning EP, de Jong M (2009) Peptide receptor imaging of prostate cancer with radiolabelled bombesin analogues. Methods 48(2):200–204

    Article  CAS  Google Scholar 

  4. De Vincentis G, Remediani S, Varvarigou AD, Di Santo G, Iori F, Laurenti C, Scopinaro F (2004) Role of 99mTc-bombesin scan in diagnosis and staging of prostate cancer. Cancer Biother Radiopharm 19(1):81–84

    Article  Google Scholar 

  5. Jadvar H (2011) Prostate cancer: PET with 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline. J Nucl Med 52(1):81–89

    Article  Google Scholar 

  6. De Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJA (2002) Visualization of prostate cancer with 11C-choline positron emission tomography. Eur Urol 42(1):18–23

    Article  Google Scholar 

  7. Plathow C, Weber WA (2008) Tumor cell metabolism imaging. J Nucl Med 49(Suppl 2):43S–63S

    Article  CAS  Google Scholar 

  8. Hong H, Zhang Y, Sun J, Cai W (2010) Positron emission tomography imaging of prostate cancer. Amino Acids 39(1):11–27

    Article  CAS  Google Scholar 

  9. Reubi JC (2003) Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 24(4):389–427

    Article  CAS  Google Scholar 

  10. Okarvi SM (2004) Peptide-based radiopharmaceuticals: future tools for diagnostic imaging of cancers and other diseases. Med Res Rev 24(3):357–397

    Article  CAS  Google Scholar 

  11. Smith CJ, Volkert WA, Hoffman TJ (2005) Radiolabeled peptide conjugates for targeting of the bombesin receptor superfamily subtypes. Nucl Med Biol 32(7):733–740

    Article  CAS  Google Scholar 

  12. Faintuch BL, Teodoro R, Duatti A, Muramoto E, Faintuch S, Smith CJ (2008) Radiolabeled bombesin analogs for prostate cancer diagnosis: preclinical studies. Nucl Med Biol 35(4):401–411

    Article  CAS  Google Scholar 

  13. de Aguiar Ferreira C, Fuscaldi LL, Townsend DM, Rubello D, de Barros ALB (2017) Radiolabeled bombesin derivatives for preclinical oncological imaging. Biomed Pharmacother 87:58–72

    Article  Google Scholar 

  14. Smith C, Volkert W, Hoffman T (2003) Gastrin releasing peptide (GRP) receptor targeted radiopharmaceuticals: a concise update. Nucl Med Biol 30(8):861–868

    Article  CAS  Google Scholar 

  15. Nock BA, Nikolopoulou A, Galanis A, Cordopatis P, Waser B, Reubi J-C, Maina T (2005) Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. J Med Chem 48(1):100–110

    Article  CAS  Google Scholar 

  16. Van de Wiele C, Dumont F, Broecke RV, Oosterlinck W, Cocquyt V, Serreyn R, Peers S, Thornback J, Slegers G, Dierckx RA (2000) Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study. Eur J Nucl Med Mol Imaging 27(11):1694–1699

    Article  Google Scholar 

  17. Van de Wiele C, Phonteyne P, Pauwels P, Goethals I, Van den Broecke R, Cocquyt V, Dierckx RA (2008) Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry. J Nucl Med 49(2):260–264

    Article  Google Scholar 

  18. Däpp S, Garayoa EG, Maes V, Brans L, Tourwé DA, Müller C, Schibli R (2011) PEGylation of 99mTc-labeled bombesin analogues improves their pharmacokinetic properties. Nucl Med Biol 38(7):997–1009

    Article  Google Scholar 

  19. García Garayoa E, Schweinsberg C, Maes V, Brans L, Bläuenstein P, Tourwé DA, Schibli R, Schubiger PA (2008) Influence of the molecular charge on the biodistribution of bombesin analogues labeled with the [99mTc(CO)3]-core. Bioconjug Chem 19(12):2409–2416

    Article  Google Scholar 

  20. Schweinsberg C, Maes V, Brans L, Bläuenstein P, Tourwé DA, Schubiger PA, Schibli R, Garayoa EG (2008) Novel glycated [99mTc(CO)3]-labeled bombesin analogues for improved targeting of gastrin-releasing peptide receptor-positive tumors. Bioconjug Chem 19(12):2432–2439

    Article  CAS  Google Scholar 

  21. de Barros ALB, das Graças Mota L, de Aguiar Ferreira C, Corrêa NCR, de Góes AM, Oliveira MC, Cardoso VN (2013) 99mTc-labeled bombesin analog for breast cancer identification. J Radioanal Nucl Chem 295(3):2083–2090

    Article  CAS  Google Scholar 

  22. Liolios CC, Fragogeorgi EA, Zikos C, Loudos G, Xanthopoulos S, Bouziotis P, Paravatou-Petsotas M, Livaniou E, Varvarigou AD, Sivolapenko GB (2012) Structural modifications of 99mTc-labelled bombesin-like peptides for optimizing pharmacokinetics in prostate tumor targeting. Int J Pharm 430(1):1–17

    Article  CAS  Google Scholar 

  23. Baidoo KE, Lin K-S, Zhan Y, Finley P, Scheffel U, Wagner HN (1998) Design, synthesis, and initial evaluation of high-affinity technetium bombesin analogues. Bioconjug Chem 9(2):218–225

    Article  CAS  Google Scholar 

  24. de Barros ALB, das Graças Mota L, de Aguiar Ferreira C, de Oliveira MC, de Góes AM, Cardoso VN (2010) Bombesin derivative radiolabeled with technetium-99m as agent for tumor identification. Bioorg Med Chem Lett 20(21):6182–6184

    Article  Google Scholar 

  25. Shi J, Jia B, Liu Z, Yang Z, Yu Z, Chen K, Chen X, Liu S, Wang F (2008) 99mTc-labeled bombesin (7–14) NH2 with favorable properties for SPECT imaging of colon cancer. Bioconjug Chem 19(6):1170–1178

    Article  CAS  Google Scholar 

  26. Brans L, Maes V, García-Garayoa E, Schweinsberg C, Daepp S, Bläuenstein P, August Schubiger P, Schibli R, Tourwé DA (2008) Glycation methods for bombesin analogs containing the (NaHis) Ac chelator for 99mTc(CO)3 radiolabeling. Chem Biol Drug Des 72(6):496–506

    Article  CAS  Google Scholar 

  27. Breeman WAP, de Jong M, Erion JL, Bugaj JE, Srinivasan A, Bernard BF, Kwekkeboom DJ, Visser TJ, Krenning EP (2002) Preclinical comparison of 111In-labeled DTPA- or DOTA-bombesin analogs for receptor-targeted scintigraphy and radionuclide therapy. J Nucl Med 43(12):1650–1656

    CAS  Google Scholar 

  28. de Visser M, Bernard HF, Erion JL, Schmidt MA, Srinivasan A, Waser B, Reubi J-C, Krenning EP, de Jong M (2007) Novel 111In-labelled bombesin analogues for molecular imaging of prostate tumours. Eur J Nucl Med Mol Imaging 34(8):1228–1238

    Article  Google Scholar 

  29. Okarvi SM, Jammaz IA (2012) Preparation and evaluation of bombesin peptide derivatives as potential tumor imaging agents: effects of structure and composition of amino acid sequence on in vitro and in vivo characteristics. Nucl Med Biol 39(6):795–804

    Article  CAS  Google Scholar 

  30. King R, Surfraz MB-U, Finucane C, Biagini SCG, Blower PJ, Mather SJ (2009) 99mTc-HYNIC-gastrin peptides: assisted coordination of 99mTc by amino acid side chains results in improved performance both in vitro and in vivo. J Nucl Med 50(4):591–598

    Article  CAS  Google Scholar 

  31. Sadeghzadeh N, Ahmadzadeh M, Erfani M (2013) Evaluation of a new radiolabeled bombesin derivative with 99mTc as potential targeted tumor imaging agent. J Radioanal Nucl Chem 298(1):287–293

    Article  CAS  Google Scholar 

  32. Shirmardi S, Gandomkar M, Mazidi M, Shafiei M, Maragheh MG (2011) Synthesis and evaluation of a new bombesin analog labeled with 99mTc as a GRP receptor imaging agent. J Radioanal Nucl Chem 288(2):327–335

    Article  CAS  Google Scholar 

  33. Sadeghzadeh N, Gandomkar M, Najafi R, Shafiei M, Ebrahimi SS, Shafiee A, Larijani B (2010) Preparation and evaluation of a new 99mTc labeled bombesin derivative for tumor imaging. J Radioanal Nucl Chem 283(1):181–187

    Article  CAS  Google Scholar 

  34. Meszaros LK, Dose A, Biagini SCG, Blower PJ (2011) Synthesis and evaluation of analogues of HYNIC as bifunctional chelators for technetium. Dalton Trans 40(23):6260–6267

    Article  CAS  Google Scholar 

  35. Zhang Y-M, Liu N, Zhu Z-H, Rusckowski M, Hnatowich DJ (2000) Influence of different chelators (HYNIC, MAG3 and DTPA) on tumor cell accumulation and mouse biodistribution of technetium-99m labeled to antisense DNA. Eur J Nucl Med 27(11):1700–1707

    Article  CAS  Google Scholar 

  36. Decristoforo C, Mather SJ (2002) The influence of chelator on the pharmacokinetics of 99mTc-labelled peptides. Q J Nucl Med 46(3):195

    CAS  Google Scholar 

  37. Teodoro R, Faintuch BL, Núñez EGF, Queiróz RG (2011) Neurotensin (8–13) analogue: radiolabeling and biological evaluation using different chelators. Nucl Med Biol 38(1):113–120

    Article  CAS  Google Scholar 

  38. Omrani HG, Rezazadeh F, Sadeghzadeh N (2017) Preparation and radiochemical evaluation of 99mTc-HYNIC-[Lys3, Tyr4] bombesin (3–14) for prostate cancer detection. J Mazandaran Univ Med Sci 26(144):367–372 (Persian)

    Google Scholar 

  39. Bauer R, Pabst H-W (1982) Tc-generators: yield of 99mTc and ratio to inactive 99Tc. Eur J Nucl Med 7(1):35–36

    Article  CAS  Google Scholar 

  40. Maina T, Nock B, Nikolopoulou A, Sotiriou P, Loudos G, Maintas D, Cordopatis P, Chiotellis E (2002) [99mTc]demotate, a new 99mTc-based [Tyr3]octreotate analogue for the detection of somatostatin receptor-positive tumours: synthesis and preclinical results. Eur J Nucl Med 29:742–753

    Article  CAS  Google Scholar 

  41. Welling MM, Visentin R, Feitsma HIJ, Lupetti A, Pauwels EKJ, Nibbering PH (2004) Infection detection in mice using 99mTc-labeled HYNIC and N2S2 chelate conjugated to the antimicrobial peptide UBI 29-41. Nucl Med Biol 31(4):503–509

    Article  CAS  Google Scholar 

  42. De K, Banerjee I, Sinha S, Ganguly S (2017) Synthesis and exploration of novel radiolabeled bombesin peptides for targeting receptor positive tumor. Peptides. https://doi.org/10.1016/j.peptides.2017.01.002

    Google Scholar 

  43. Santos-Cuevas CL, Ferro-Flores G, de Murphy CA, Ramírez FdM, Luna-Gutiérrez MA, Pedraza-López M, García-Becerra R, Ordaz-Rosado D (2009) Design, preparation, in vitro and in vivo evaluation of 99mTc-N2S2-Tat (49–57)-bombesin: a target-specific hybrid radiopharmaceutical. Int J Pharm 375(1):75–83

    Article  CAS  Google Scholar 

  44. Varasteh Z, Velikyan I, Lindeberg G, Sörensen J, Larhed M, Sandström M, Selvaraju RK, Malmberg J, Tolmachev V, Orlova A (2013) Synthesis and characterization of a high-affinity NOTA-conjugated bombesin antagonist for GRPR-targeted tumor imaging. Bioconjug Chem 24(7):1144–1153

    Article  CAS  Google Scholar 

  45. Ferro-Flores G, de Murphy CA, Rodriguez-Cortes J, Pedraza-Lopez M, Ramrez-Iglesias MT (2006) Preparation and evaluation of 99mTc-EDDA/HYNIC-[Lys3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumours. Nucl Med Commun 27(4):371–376

    Article  CAS  Google Scholar 

  46. Ananias HJ, Yu Z, Dierckx RA, van der Wiele C, Helfrich W, Wang F, Yan Y, Chen X, de Jong IJ, Elsinga PH (2011) 99mTechnetium-HYNIC(tricine/TPPTS)-Aca-bombesin (7–14) as a targeted imaging agent with microSPECT in a PC-3 prostate cancer xenograft model. Mol Pharm 8(4):1165–1173

    Article  CAS  Google Scholar 

  47. Ferro-Flores G, Luna-Gutiérrez M, Ocampo-García B, Santos-Cuevas C, Azorín-Vega E, Jiménez-Mancilla N, Orocio-Rodríguez E, Davanzo J, García-Pérez FO (2017) Clinical translation of a PSMA inhibitor for 99mTc-based SPECT. Nucl Med Biol 48(6):36–44

    Article  CAS  Google Scholar 

  48. Xu X, Zhang J, Hu S, He S, Bao X, Ma G, Luo J, Cheng J, Zhang Y (2017) 99mTc-labeling and evaluation of a HYNIC modified small-molecular inhibitor of prostate-specific membrane antigen. Nucl Med Biol 48(6):69–75

    Article  CAS  Google Scholar 

  49. Santos-Cuevas C, Davanzo J, Ferro-Flores G, García-Pérez FO, Ocampo-García B, Ignacio-Alvarez E, Gómez-Argumosa E, Pedraza-López M (2017) 99mTc-labeled PSMA inhibitor: biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients. Nucl Med Biol 52(9):1–6

    Article  CAS  Google Scholar 

  50. Liolios CC, Fragogeorgi EA, Zikos C, Loudos G, Xanthopoulos S, Bouziotis P, Paravatou-Petsotas M, Livaniou E, Varvarigou AD, Sivolapenko GB (2012) Structural modifications of 99mTc-labelled bombesin-like peptides for optimizing pharmacokinetics in prostate tumor targeting. Int J Pharm 430:1–17

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was part of the PhD Thesis of Mohsen Mohammadgholi and was supported by a Grant (No. 1392) from Mazandaran University of Medical Sciences, Sari, Iran. We would also like to thank Dr. Hassan Ghorbantabar Omrani for his help with the preparation of 99m-Technetium from Hazrat Fatemeh Zahra Heart Centre.

Author information

Authors and Affiliations

  1. Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Mohsen Mohammadgholi, Farzaneh Rezazadeh, Iman Emrarian & Nourollah Sadeghzadeh

  2. Immunogenetics Research Centre, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Saeid Abediankenari & Narjes Jafari

  3. Department of Radiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Seyed Mohammad Abedi

  4. North Research Centre-Pasteur Institute of Iran, Amol, Iran

    Ramezan Behzadi

Authors
  1. Mohsen Mohammadgholi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Farzaneh Rezazadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saeid Abediankenari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seyed Mohammad Abedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Iman Emrarian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Narjes Jafari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ramezan Behzadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nourollah Sadeghzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nourollah Sadeghzadeh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadgholi, M., Rezazadeh, F., Abediankenari, S. et al. Evaluation of new 99mTc-labeled HYNIC-bombesin analogue for prostate cancer imaging. J Radioanal Nucl Chem 316, 595–607 (2018). https://doi.org/10.1007/s10967-018-5819-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10967-018-5819-z

Keywords

Search

Navigation