[99mTc]Demotate, a new 99mTc-based [Tyr3]octreotate analogue for the detection of somatostatin receptor-positive tumours: synthesis and preclinical results
| Autor: | Paul Cordopatis, D Maintas, Anastasia Nikolopoulou, Theodosia Maina, Petros Sotiriou, Berthold A. Nock, Efstratios Chiotellis, George Loudos |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Metabolic Clearance Rate Mice Nude Octreotide In Vitro Techniques Peptides Cyclic Sensitivity and Specificity Mice chemistry.chemical_compound In vivo Internal medicine Tumor Cells Cultured Radioligand medicine Animals Tissue Distribution Radiology Nuclear Medicine and imaging Receptors Somatostatin Rats Wistar Radionuclide Imaging Receptor IC50 Somatostatin Receptor Positive Cerebral Cortex Octreotate Somatostatin receptor Reproducibility of Results Organotechnetium Compounds General Medicine Molecular biology Rats Pancreatic Neoplasms Endocrinology Models Chemical chemistry Isotope Labeling Female Protein Binding medicine.drug |
| Zdroj: | European Journal of Nuclear Medicine and Molecular Imaging. 29:742-753 |
| ISSN: | 1619-7089 1619-7070 |
| DOI: | 10.1007/s00259-002-0782-9 |
| Popis: | 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 (IC(50)=0.13 n M) 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 ( K(d)=0.07 n M) 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. |
| Databáze: | OpenAIRE |
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