Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer 177Lu-AMBA

  • Beatrice Waser
  • Véronique Eltschinger
  • Karen Linder
  • Adrian Nunn
  • Jean Claude Reubi
Original article

Abstract

Purpose

To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, 177Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3.

Methods

In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand 177Lu-AMBA was used and compared with established bombesin radioligands such as 125I-Tyr4-bombesin and 125I-[D-Tyr6,β-Ala11,Phe13,Nle14]-bombesin(6–14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour.

Results

177Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. 177Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with 177Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with 177Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with 177Lu-AMBA than with the conventional bombesin radioligands.

Conclusion

The present in vitro study suggests that 177Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessels.

Keywords

Receptor binding Radiopharmacy Tumour targeting Molecular imaging Radiolabelled peptides 

Notes

Acknowledgements

We thank Dr. Jiaqing Chen for 177Lu-AMBA tracer preparation.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Beatrice Waser
    • 1
  • Véronique Eltschinger
    • 1
  • Karen Linder
    • 2
  • Adrian Nunn
    • 2
  • Jean Claude Reubi
    • 1
  1. 1.Division of Cell Biology and Experimental Cancer Research, Institute of PathologyUniversity of BerneBernSwitzerland
  2. 2.Bracco Research USA IncPrincetonUSA

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