摘要：

Demobesin 1 is a potent new GRP-R-selective bombesin (BN) analogue containing an open chain tetraamine chelator for stable technetium-99m binding. Following a convenient labelling protocol, the radiopeptide, [[sup 99m]Tc]Demobesin 1, formed in nearly quantitative yields and with high specific activities. Both unlabelled and labelled peptide demonstrated high-affinity binding in membrane preparations of the human androgen-independent prostate adenocarcinoma PC-3 cell line. The IC[sub 50] values determined for Demobesin 1 and [Tyr[sup 4]]BN were 0.70 ± 0.08 nM and 1.5 ± 0.20 nM, respectively, while the K[sub d] defined for [[sup 99m]Tc/[sup 99g]Tc]Demobesin 1 was 0.67 ± 0.10 nM. [[sup 99m]Tc]Demobesin 1 was rather stable in murine plasma, whereas it degraded rapidly in kidney and liver homogenates. After injection in healthy Swiss albino mice, [[sup 99m]Tc]Demobesin 1 accumulated very efficiently in the target organs (pancreas, intestinal tract) via a GRP-R-mediated process, as shown by in vivo receptor blocking experiments. An equally high and GRP-R-mediated uptake was exhibited by [[sup 99m]Tc]Demobesin 1 after injection in PC-3 tumour-bearing athymic mice. The initial high radioligand uptake of 16.2 ± 3.1%ID/g in the PC3 xenografts at 1 h p.i. remained at a similar level (15.61 ± 1.19%ID/g) at 4 h p.i. Even after 24 h p.i., when the radioactivity had cleared from all other tissues, a value of 5.24 ± 0.67%ID/g was still observed in the tumour. The high and prolonged localization of [[sup 99m]Tc]Demobesin 1 at the tumour site and its rapid background clearance are very promising qualities for GRP-R-targeted tumour imaging in man.

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