Linked Life Data

20066690

Source:http://linkedlifedata.com/resource/pubmed/id/20066690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2010-2-15
pubmed:abstractText
Owing to its optimal nuclear properties, ready availability, low cost and favourable dosimetry, (99m)Tc continues to be the ideal radioisotope for medical-imaging applications. Bifunctional chelators based on a tetraamine framework exhibit facile complexation with Tc(V)O(2) to form monocationic species with high in vivo stability and significant hydrophilicity, which leads to favourable pharmacokinetics. The synthesis of a series of 1,4,8,11-tetraazaundecane derivatives (01-06) containing different functional groups at the 6-position for the conjugation of biomolecules and subsequent labelling with (99m)Tc is described herein. The chelator 01 was used as a starting material for the facile synthesis of chelators functionalised with OH (02), N(3) (04) and O-succinyl ester (05) groups. A straightforward and easy synthesis of carboxyl-functionalised tetraamine-based chelator 06 was achieved by using inexpensive and commercially available starting materials. Conjugation of 06 to a potent bombesin-antagonist peptide and subsequent labelling with (99m)Tc afforded the radiotracer (99m)Tc-N4-BB-ANT, with radiolabelling yields of >97% at a specific activity of 37 GBq micromol(-1). An IC(50) value of (3.7+/-1.3) nM was obtained, which confirmed the high affinity of the conjugate to the gastrin-releasing-peptide receptor (GRPr). Immunofluorescence and calcium mobilisation assays confirmed the strong antagonist properties of the conjugate. In vivo pharmacokinetic studies of (99m)Tc-N4-BB-ANT showed high and specific uptake in PC3 xenografts and in other GRPr-positive organs. The tumour uptake was (22.5+/-2.6)% injected activity per gram (% IA g(-1)) at 1 h post injection (p.i.). and increased to (29.9+/-4.0)% IA g(-1) at 4 h p.i. The SPECT/computed tomography (CT) images showed high tumour uptake, clear background and negligible radioactivity in the abdomen. The promising preclinical results of (99m)Tc-N4-BB-ANT warrant its potential candidature for clinical translation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1521-3765
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2115-24
pubmed:meshHeading
pubmed-meshheading:20066690-Amino Acid Sequence, pubmed-meshheading:20066690-Animals, pubmed-meshheading:20066690-Antineoplastic Agents, pubmed-meshheading:20066690-Bombesin, pubmed-meshheading:20066690-Cell Line, Tumor, pubmed-meshheading:20066690-Chelating Agents, pubmed-meshheading:20066690-Gastrin-Releasing Peptide, pubmed-meshheading:20066690-Humans, pubmed-meshheading:20066690-Isotope Labeling, pubmed-meshheading:20066690-Mice, pubmed-meshheading:20066690-Mice, Nude, pubmed-meshheading:20066690-Molecular Structure, pubmed-meshheading:20066690-Neoplasms, pubmed-meshheading:20066690-Organotechnetium Compounds, pubmed-meshheading:20066690-Polyamines, pubmed-meshheading:20066690-Radiopharmaceuticals, pubmed-meshheading:20066690-Technetium, pubmed-meshheading:20066690-Tomography, Emission-Computed, Single-Photon
pubmed:year
2010
pubmed:articleTitle
Tetraamine-derived bifunctional chelators for technetium-99m labelling: synthesis, bioconjugation and evaluation as targeted SPECT imaging probes for GRP-receptor-positive tumours.
pubmed:affiliation
Division of Radiological Chemistry, University Hospital of Basel, 4031 Basel, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't