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

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