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Metal-ion-dependent biological properties of a chelator-derived somatostatin analogue for tumour targeting

Heppeler, A. and André, J. P. and Buschmann, I. and Wang, X. and Reubi, J. C. and Hennig, M. and Kaden, T. A. and Maecke, H. R.. (2008) Metal-ion-dependent biological properties of a chelator-derived somatostatin analogue for tumour targeting. Chemistry, a European journal, Vol. 14, H. 10. pp. 3026-3034.

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Official URL: http://edoc.unibas.ch/dok/A6006586

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Abstract

Somatostatin-based radioligands have been shown to have sensitive imaging properties for neuroendocrine tumours and their metastases. The potential of [(55)Co(dotatoc)] (dotatoc =4,7,10-tricarboxymethyl-1,4,7,10-tetraazacyclododecane-1-ylacetyl-D-Phe-(Cys-Tyr-D-Trp-Lys-Thr-Cys)-threoninol (disulfide bond)) as a new radiopharmaceutical agent for PET has been evaluated. (57)Co was used as a surrogate of the positron emitter (55)Co and the pharmacokinetics of [(57)Co(dotatoc)] were investigated by using two nude mouse models. The somatostatin receptor subtype (sst1-sst5) affinity profile of [(nat)Co(dotatoc)] on membranes transfected with human somatostatin receptor subtypes was assessed by using autoradiographic methods. These studies revealed that [(57)Co(dotatoc)] is an sst2-specific radiopeptide which presents the highest affinity ever found for the sst2 receptor subtype. The rate of internalisation into the AR4-2J cell line also was the highest found for any somatostatin-based radiopeptide. Biodistribution studies, performed in nude mice bearing an AR4-2J tumour or a transfected HEK-sst2 cell-based tumour, showed high and specific uptake in the tumour and in other sst-receptor-expressing tissues, which reflects the high receptor binding affinity and the high rate of internalisation. The pharmacologic differences between [(57)Co(dotatoc)] and [(67)Ga(dotatoc)] are discussed in terms of the structural parameters found for the chelate models [Co(II)(dota)](2-) and [Ga(III)(dota)](-) whose X-ray structures have been determined. Both chelates show six-fold coordination in pseudo-octahedral arrangements.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Radiologische Chemie (Mindt)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Ehemalige Einheiten Querschnittsfächer (Klinik) > Radiologische Chemie (Mindt)
UniBasel Contributors:Mäcke, Helmut
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley-VCH Verlag
ISSN:0947-6539
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 Apr 2014 08:01
Deposited On:25 Apr 2014 08:01

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