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

Purpose: To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, Lu-177-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 Lu-177-AMBA was used and compared with established bombesin radioligands such as I-125-Tyr(4)-bombesin and I-125-[D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]-bombesin( 6 - 14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. Results: Lu-177-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. Lu-177-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 Lu-177-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with Lu-177-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with Lu-177-AMBA than with the conventional bombesin radioligands. Conclusion: The present in vitro study suggests that Lu-177-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.