[99mtc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging

Nock, B; Nikolopoulou, A; Chiotellis, E; Loudos, G; Maintas, D; Reubi, JC; Maina, T

dc.contributor.author	Nock, B	en
dc.contributor.author	Nikolopoulou, A	en
dc.contributor.author	Chiotellis, E	en
dc.contributor.author	Loudos, G	en
dc.contributor.author	Maintas, D	en
dc.contributor.author	Reubi, JC	en
dc.contributor.author	Maina, T	en
dc.date.accessioned	2014-03-01T01:18:29Z
dc.date.available	2014-03-01T01:18:29Z
dc.date.issued	2003	en
dc.identifier.issn	1619-7070	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/15041
dc.subject	99mTc	en
dc.subject	Bombesin	en
dc.subject	Gastrin releasing peptide	en
dc.subject	Tetraamine chelator	en
dc.subject	Tumour imaging	en
dc.subject.classification	Radiology, Nuclear Medicine & Medical Imaging	en
dc.subject.other	bombesin derivative	en
dc.subject.other	demobensin 1 technetium tc 99m	en
dc.subject.other	G protein coupled receptor	en
dc.subject.other	gastrin releasing peptide receptor	en
dc.subject.other	unclassified drug	en
dc.subject.other	bombesin	en
dc.subject.other	diagnostic agent	en
dc.subject.other	drug derivative	en
dc.subject.other	gastrin releasing peptide	en
dc.subject.other	radiopharmaceutical agent	en
dc.subject.other	technetium 99m demobesin 1	en
dc.subject.other	technetium complex	en
dc.subject.other	animal experiment	en
dc.subject.other	animal model	en
dc.subject.other	article	en
dc.subject.other	binding affinity	en
dc.subject.other	cancer cell culture	en
dc.subject.other	controlled study	en
dc.subject.other	drug accumulation	en
dc.subject.other	drug clearance	en
dc.subject.other	drug degradation	en
dc.subject.other	drug distribution	en
dc.subject.other	drug potency	en
dc.subject.other	drug receptor binding	en
dc.subject.other	drug stability	en
dc.subject.other	drug tissue level	en
dc.subject.other	drug uptake	en
dc.subject.other	human	en
dc.subject.other	human cell	en
dc.subject.other	injection	en
dc.subject.other	kidney metabolism	en
dc.subject.other	liver homogenate	en
dc.subject.other	male	en
dc.subject.other	mouse	en
dc.subject.other	nonhuman	en
dc.subject.other	prostate adenocarcinoma	en
dc.subject.other	target organ	en
dc.subject.other	tumor scintiscanning	en
dc.subject.other	tumor xenograft	en
dc.subject.other	animal	en
dc.subject.other	antibody specificity	en
dc.subject.other	blood	en
dc.subject.other	cancer transplantation	en
dc.subject.other	cell culture	en
dc.subject.other	cell membrane	en
dc.subject.other	comparative study	en
dc.subject.other	evaluation	en
dc.subject.other	female	en
dc.subject.other	isotope labeling	en
dc.subject.other	kidney	en
dc.subject.other	liver	en
dc.subject.other	metabolic clearance rate	en
dc.subject.other	metabolism	en
dc.subject.other	methodology	en
dc.subject.other	pathology	en
dc.subject.other	prostate tumor	en
dc.subject.other	protein binding	en
dc.subject.other	scintiscanning	en
dc.subject.other	skeletal muscle	en
dc.subject.other	synthesis	en
dc.subject.other	tissue distribution	en
dc.subject.other	Animals	en
dc.subject.other	Bombesin	en
dc.subject.other	Cell Membrane	en
dc.subject.other	Female	en
dc.subject.other	Gastrin-Releasing Peptide	en
dc.subject.other	Humans	en
dc.subject.other	Isotope Labeling	en
dc.subject.other	Kidney	en
dc.subject.other	Liver	en
dc.subject.other	Male	en
dc.subject.other	Metabolic Clearance Rate	en
dc.subject.other	Muscle, Skeletal	en
dc.subject.other	Neoplasm Transplantation	en
dc.subject.other	Organ Specificity	en
dc.subject.other	Organotechnetium Compounds	en
dc.subject.other	Prostatic Neoplasms	en
dc.subject.other	Protein Binding	en
dc.subject.other	Radiopharmaceuticals	en
dc.subject.other	Tissue Distribution	en
dc.subject.other	Tumor Cells, Cultured	en
dc.title	[99mtc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging	en
heal.type	journalArticle	en
heal.identifier.primary	10.1007/s00259-002-1040-x	en
heal.identifier.secondary	http://dx.doi.org/10.1007/s00259-002-1040-x	en
heal.language	English	en
heal.publicationDate	2003	en
heal.abstract	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, [Tc-99m]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 IC50 values determined for Demobesin 1 and [Tyro]BN were 0.70+/-0.08 nM and 1.5+/-0.20 nM, respectively, while the K-d defined for [Tc-99m/Tc-99g]Demobesin 1 was 0.67+/-0.10 nM. [Tc-99m]Demobesin 1 was rather stable in murine plasma, whereas it degraded rapidly in kidney and liver homogenates. After injection in healthy Swiss albino mice, [Tc-99m]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 [Tc-99m]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 PC-3 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 [Tc-99m]Demobesin 1 at the tumour site and its rapid background clearance are very promising qualities for GRP-R-targeted tumour imaging in man.	en
heal.publisher	SPRINGER-VERLAG	en
heal.journalName	European Journal of Nuclear Medicine and Molecular Imaging	en
dc.identifier.doi	10.1007/s00259-002-1040-x	en
dc.identifier.isi	ISI:000181033800010	en
dc.identifier.volume	30	en
dc.identifier.issue	2	en
dc.identifier.spage	247	en
dc.identifier.epage	258	en