[Tc-99m]demotate, a new Tc-99m-based [Tyr(3)]octreotate analogue for the detection of somatostatin receptor-positive tumours: synthesis and preclinical results

Maina, T; Nock, B; Nikolopoulou, A; Sotiriou, P; Loudos, G; Maintas, D; Cordopatis, P; Chiotellis, E

dc.contributor.author	Maina, T	en
dc.contributor.author	Nock, B	en
dc.contributor.author	Nikolopoulou, A	en
dc.contributor.author	Sotiriou, P	en
dc.contributor.author	Loudos, G	en
dc.contributor.author	Maintas, D	en
dc.contributor.author	Cordopatis, P	en
dc.contributor.author	Chiotellis, E	en
dc.date.accessioned	2014-03-01T01:52:02Z
dc.date.available	2014-03-01T01:52:02Z
dc.date.issued	2002	en
dc.identifier.issn	1619-7070	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/26537
dc.subject	somatostatin receptor	en
dc.subject	tumour imaging	en
dc.subject	Tc-99m	en
dc.subject	[Tyr(3)]octreotate	en
dc.subject	tetraamine chelator	en
dc.subject.classification	Radiology, Nuclear Medicine & Medical Imaging	en
dc.subject.other	IN-VITRO	en
dc.subject.other	BINDING PEPTIDES	en
dc.subject.other	TUMORS	en
dc.subject.other	SCINTIGRAPHY	en
dc.subject.other	RADIOPHARMACEUTICALS	en
dc.subject.other	RADIOTHERAPY	en
dc.subject.other	DERIVATIVES	en
dc.subject.other	METABOLISM	en
dc.subject.other	DIAGNOSIS	en
dc.subject.other	AFFINITY	en
dc.title	[Tc-99m]demotate, a new Tc-99m-based [Tyr(3)]octreotate analogue for the detection of somatostatin receptor-positive tumours: synthesis and preclinical results	en
heal.type	journalArticle	en
heal.language	English	en
heal.publicationDate	2002	en
heal.abstract	Demotate is a new tetraamine-functionalised [Tyr(3)]octreotate derivative that binds technetium-99m with a high efficiency under mild conditions. The resulting radioligand, [Tc-99m]Demotate, forms in a high purity and is stable for at least 6 h after labelling. The affinity of the unlabelled peptide for somatostatin receptors is high (IC50=0.13 nM) and comparable to that of [Tyr(3)]octreotate or [Tyr3]octreotide, as demonstrated by competition binding experiments in rat brain cortex or AR42J cell membrane preparations. An equally very high affinity (K-d=0.07 nM) was exhibited by [Tc-99m/Tc-99g]Demotate during saturation binding experiments using rat brain cortex membrane homogenates. The radioligand resisted hydrolytic degradation in mouse plasma and was excreted intact in mouse urine. In vivo, [Tc-99m]Demotate cleared very rapidly from non-target tissues into the bladder via the kidneys, while radioactivity uptake in target organs was very high. In mice bearing the experimental AR42J tumour, [99mTc]Demotate demonstrated a very high tumour uptake at I h p.i. (25%ID/g) that remained high (20%ID/g) at 4 h p.i. This uptake could be effectively blocked by co-injection of a high dose of [Tyr3]octreotate together with the radioligand. High-quality planar and single-photon emission tomographic images were acquired 1 h after injection of [Tc-99m]Demotate in tumour-bearing mice, illustrating the excellent properties of this agent for somatostatin receptor tumour imaging.	en
heal.publisher	SPRINGER-VERLAG	en
heal.journalName	EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING	en
dc.identifier.isi	ISI:000176324700005	en
dc.identifier.volume	29	en
dc.identifier.issue	6	en
dc.identifier.spage	742	en
dc.identifier.epage	753	en