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- Title
[[sup 99m] Tc]Demotate, a new [sup 99m] Tc-based [Tyr[sup 3] ]octreotate analogue for the detection of somatostatin receptor-positive tumours: synthesis and preclinical results.
- Authors
Maina, Theodosia; Nock, Berthold; Nikolopoulou, Anastasia; Sotiriou, Petros; Loudos, George; Maintas, Dimitrios; Cordopatis, Paul; Chiotellis, Efstratios
- Abstract
Demotate is a new tetraamine-functionalised [Tyr³]octreotate derivative that binds technetium-99m with a high efficiency under mild conditions. The resulting radioligand, [[sup 99m]Tc]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 (IC[sup 50]=0.13 nM) and comparable to that of [Tyr&sup3']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[sub d]=0.07 nM) was exhibited by [[sup 99m]Tc/[sup 99g]Tc]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, [[sup 99m]Tc]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, [[sup 99m]Tc]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 [[sup 99m]Tc]Demotate in tumour-bearing mice, illustrating the excellent properties of this agent for somatostatin receptor tumour imaging.
- Subjects
TECHNETIUM isotopes; TUMOR diagnosis; SOMATOSTATIN; CLINICAL chemistry
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2002, Vol 29, Issue 6, p742
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-002-0782-9