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

Waser, Beatrice ; Eltschinger, Véronique ; Linder, Karen ; Nunn, Adrian ; Reubi, Jean

In: European Journal of Nuclear Medicine and Molecular Imaging, 2007, vol. 34, no. 1, p. 95-100

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    Title
    • Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer 177Lu-AMBA
    Author
    • Waser, Beatrice. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, P.O. Box 62, 3010, Bern, Switzerland
    • Eltschinger, Véronique. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, P.O. Box 62, 3010, Bern, Switzerland
    • Linder, Karen. Bracco Research USA Inc, Princeton, NJ, USA
    • Nunn, Adrian. Bracco Research USA Inc, Princeton, NJ, USA
    • Reubi, Jean. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, P.O. Box 62, 3010, Bern, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • European Journal of Nuclear Medicine and Molecular Imaging, 2007, vol. 34, no. 1, p. 95-100. Springer-Verlag
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:310156
    Summary
    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