[99mTc]Demotate, a new 99mTc-based [Tyr3]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	2014-03-01T01:17:20Z
dc.date.available	2014-03-01T01:17:20Z
dc.date.issued	2002	en
dc.identifier.issn	03406997	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/14463
dc.subject	99mTc	en
dc.subject	[Tyr3]octreotate	en
dc.subject	Somatostatin receptor	en
dc.subject	Tetraamine chelator	en
dc.subject	Tumour imaging	en
dc.subject.other	demotate tc 99m	en
dc.subject.other	octreotate[3 tyrosine]	en
dc.subject.other	octreotide[3 tyrosine]	en
dc.subject.other	somatostatin receptor	en
dc.subject.other	technetium 99m	en
dc.subject.other	tyrosine derivative	en
dc.subject.other	unclassified drug	en
dc.subject.other	3 Tyr octreotide	en
dc.subject.other	3-Tyr-octreotide	en
dc.subject.other	cyclopeptide	en
dc.subject.other	diagnostic agent	en
dc.subject.other	drug derivative	en
dc.subject.other	octreotate, Tyr(3)	en
dc.subject.other	octreotate, Tyr(3)-	en
dc.subject.other	octreotide	en
dc.subject.other	octreotide, iodoTyr(3)	en
dc.subject.other	octreotide, iodoTyr(3)-	en
dc.subject.other	somatostatin receptor 2	en
dc.subject.other	technetium complex	en
dc.subject.other	technetium Tc 99m demotate	en
dc.subject.other	amine	en
dc.subject.other	demotate	en
dc.subject.other	animal cell	en
dc.subject.other	animal model	en
dc.subject.other	animal tissue	en
dc.subject.other	article	en
dc.subject.other	brain cortex	en
dc.subject.other	brain homogenate	en
dc.subject.other	cell membrane	en
dc.subject.other	controlled study	en
dc.subject.other	drug clearance	en
dc.subject.other	drug degradation	en
dc.subject.other	drug distribution	en
dc.subject.other	drug stability	en
dc.subject.other	drug synthesis	en
dc.subject.other	drug uptake	en
dc.subject.other	female	en
dc.subject.other	high performance liquid chromatography	en
dc.subject.other	IC 50	en
dc.subject.other	in vivo study	en
dc.subject.other	internalization	en
dc.subject.other	isotope labeling	en
dc.subject.other	male	en
dc.subject.other	mouse	en
dc.subject.other	nonhuman	en
dc.subject.other	radioactivity	en
dc.subject.other	rat	en
dc.subject.other	receptor affinity	en
dc.subject.other	single photon emission computer tomography	en
dc.subject.other	animal	en
dc.subject.other	cell culture	en
dc.subject.other	chemical model	en
dc.subject.other	in vitro study	en
dc.subject.other	metabolic clearance rate	en
dc.subject.other	metabolism	en
dc.subject.other	methodology	en
dc.subject.other	nude mouse	en
dc.subject.other	pancreas tumor	en
dc.subject.other	protein binding	en
dc.subject.other	reproducibility	en
dc.subject.other	scintiscanning	en
dc.subject.other	sensitivity and specificity	en
dc.subject.other	synthesis	en
dc.subject.other	tissue distribution	en
dc.subject.other	Wistar rat	en
dc.subject.other	animal experiment	en
dc.subject.other	imaging	en
dc.subject.other	tumor	en
dc.subject.other	Animals	en
dc.subject.other	Cerebral Cortex	en
dc.subject.other	Female	en
dc.subject.other	Isotope Labeling	en
dc.subject.other	Male	en
dc.subject.other	Metabolic Clearance Rate	en
dc.subject.other	Mice	en
dc.subject.other	Mice, Nude	en
dc.subject.other	Models, Chemical	en
dc.subject.other	Octreotide	en
dc.subject.other	Organotechnetium Compounds	en
dc.subject.other	Pancreatic Neoplasms	en
dc.subject.other	Peptides, Cyclic	en
dc.subject.other	Protein Binding	en
dc.subject.other	Rats	en
dc.subject.other	Rats, Wistar	en
dc.subject.other	Receptors, Somatostatin	en
dc.subject.other	Reproducibility of Results	en
dc.subject.other	Sensitivity and Specificity	en
dc.subject.other	Tissue Distribution	en
dc.subject.other	Tumor Cells, Cultured	en
dc.title	[99mTc]Demotate, a new 99mTc-based [Tyr3]octreotate analogue for the detection of somatostatin receptor-positive tumours: Synthesis and preclinical results	en
heal.type	journalArticle	en
heal.identifier.primary	10.1007/s00259-002-0782-9	en
heal.identifier.secondary	http://dx.doi.org/10.1007/s00259-002-0782-9	en
heal.publicationDate	2002	en
heal.abstract	Demotate is a new tetraamine-functionalised [Tyr3]octreotate derivative that binds technetium-99m with a high efficiency under mild conditions. The resulting radioligand, [99mTc]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 [Tyr3]octreotate or [Tyr3]octreotide, as demonstrated by competition binding experiments in rat brain cortex or AR42J cell membrane preparations. An equally very high affinity (Kd=0.07 nM) was exhibited by [99mTc/99gTc]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, [99mTc]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 1 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 [99mTc]Demotate in tumour-bearing mice, illustrating the excellent properties of this agent for somatostatin receptor tumour imaging.	en
heal.journalName	European Journal of Nuclear Medicine	en
dc.identifier.doi	10.1007/s00259-002-0782-9	en
dc.identifier.volume	29	en
dc.identifier.issue	6	en
dc.identifier.spage	742	en
dc.identifier.epage	753	en