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Investigational New Drugs

, Volume 32, Issue 1, pp 37–46 | Cite as

Rhodamine-marked bombesin: a novel means for prostate cancer fluorescence imaging

  • Alexander SturzuEmail author
  • Sumbla Sheikh
  • Hartmut Echner
  • Thomas Nägele
  • Martin Deeg
  • Bushra Amin
  • Christian Schwentner
  • Marius Horger
  • Ulrike Ernemann
  • Stefan Heckl
PRECLINICAL STUDIES

Summary

The gastrin releasing peptide receptor (GRPR) has been found to be strongly expressed in various types of cancers such as prostate and breast carcinomas. The GRPR ligands gastrin releasing peptide and bombesin can play a very significant role in cancer therapy and diagnostics. In this study we synthesized unlabeled bombesin BBN along with two conjugates in which the correct bombesin (BBN-Rhd) and a mutant bombesin (mBBN-Rhd) sequence was coupled to rhodamine, a fluorescent dye. These novel rhodamine fluorescent conjugates were used to study the targeting and uptake of bombesin on a cellular level. Nine different human cell lines including both tumor and healthy cells were examined using flow cytometry and confocal laser scanning microscopy. GRPR mRNA expression analysis was performed and it was found that the receptor is highly expressed in LNCaP and PC3 cells compared to the rest of other cell lines. Competition experiments were performed to verify the receptor dependence of the labeled conjugates using unmarked bombesin. The present study is a first attempt at direct fluorescence imaging of living cells using bombesin and its target, the GRPR. A rhodamine bombesin conjugate can be used as marker to differentiate between healthy cells and malignant cells such as prostate hyperplasia and prostate carcinoma in the early detection of cancer.

Keywords

Gastrin releasing peptide receptor Bombesin Ligands Fluorescence imaging conjugates 

Notes

Acknowledgments

This study has been supported by the Wilhelm-Sander-Foundation and the Interdisciplinary Centre for Clinical Research, University of Tübingen.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Alexander Sturzu
    • 1
    • 2
    Email author
  • Sumbla Sheikh
    • 2
  • Hartmut Echner
    • 2
  • Thomas Nägele
    • 1
  • Martin Deeg
    • 3
  • Bushra Amin
    • 2
  • Christian Schwentner
    • 4
  • Marius Horger
    • 5
  • Ulrike Ernemann
    • 1
  • Stefan Heckl
    • 1
  1. 1.Department of NeuroradiologyUniversity of TübingenTübingenGermany
  2. 2.Peptide Synthesis Laboratory, Interfaculty Institute of BiochemistryUniversity of TübingenTübingenGermany
  3. 3.Mass Spectrometry Laboratory, Medicinal Research CentreUniversity of TübingenTübingenGermany
  4. 4.Department of UrologyUniversity of TübingenTübingenGermany
  5. 5.Department of RadiologyUniversity of TübingenTübingenGermany

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