ArticleEuropean journal of nuclear medicine and molecular imaging2007
[99mTc]Demotensin 5 and 6 in the NTS1-R-targeted imaging of tumours: synthesis and preclinical results.
Article in European journal of nuclear medicine and molecular imaging, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 45 citations in OpenAlex.
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6 authors at 2 institutions in 1 country.
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Abstract
purposeThe aim of this study was to evaluate the applicability of [(99m)Tc]Demotensin 5 and 6 [Formula: see text] in the targeted diagnostic imaging of neurotensin subtype 1 receptor (NTS1-R)-expressing tumours.
methodsLabelling of Demotensin 5 and 6 with (99m)Tc was conducted by brief incubation with (99m)TcO(4) (-), SnCl(2) and citrate anions in alkaline medium at ambient temperature. Affinities of conjugates for the NTS1-R were determined by competition binding experiments in WiDr cell membranes using [(125)I-Tyr(3)]NT as the radioligand. Saturation binding assays were conducted for [(99m)Tc/(99g)Tc]Demotensin 6 in WiDr cell membranes. Internalisation of [(99m)Tc]Demotensin 5 and 6 was studied at 37 degrees C in WiDr cells. Biodistribution of [(99m)Tc]Demotensin 5 and 6 was performed in female Swiss nu/nu mice bearing human WiDr xenografts.
resultsUnlabelled conjugates showed a high affinity for the human NTS1-R (Demotensin 5 IC(50)=0.03+/-0.01 nM; Demotensin 6 IC(50)=0.08+/-0.02 nM), while high affinity was also exhibited by (radio)metallated [(99m)Tc/(99g)Tc]Demotensin 6 (K (d)=0.13+/-0.01 nM). [(99m)Tc]Demotensin 5 and 6 internalised rapidly and specifically in WiDr cells. After injection in WiDr tumour-bearing mice, radiopeptides, and especially the doubly stabilised [(99m)Tc]Demotensin 6, showed NTS1-R-mediated uptake in the intestines and in the implanted tumour (4.30+/-0.45%ID/g at 1 h post injection) and rapid renal excretion from non-target tissues into the urine.
conclusion[(99m)Tc]Demotensin 6 shows a favourable preclinical profile and further testing in patients is warranted to monitor its eventual applicability as a radiotracer in the diagnostic imaging of NTS1-R-positive tumours.
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