A monoreactive DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) prochelator (4,7,10-tricarboxymethyl-tert-butyl ester 1,4,7,10-tetraazacyclododecane-1-acetate) was synthesised which is useful in solidphase and solution-phase peptide synthesis; it was coupled to the somatostatin analogue Tyr -octreotide. The new compound delineates SRIF-receptor positive tumours very favourably and shows distinctly lower uptake by the kidneys. Evidently, the differences in the coordination chemistry of the metals causes the differences in the biological behaviour. Indeed, a crystallographic study of the Ga 3 and Y 3 complexes of the model peptide DOTA-d-PheNH 2 showed differences in the geometry of the complexes. The gallium complex is hexacoordinated with pseudooctahedral cis geometry and a folded macrocyclic unit. The equatorial plane is formed by two transannular nitrogens of the cyclen ring and two oxygens of the corresponding carboxylate groups. The two axial positions are formed by the two remaining ring nitrogen atoms. The amide carboxy oxygen is not bound to the metal and one carboxylate group is free and most likely contributes to the favourable handling of the radiopeptide by the kidneys. In contrast, the structure of Y-DOTA-dPheNH 2 has eight-fold coordination, and includes the amide carboxy oxygen. The geometry is a compact and somewhat distorted square-antiprism with two almost perfect planes (N4 and O4) with a maximum deviation of 0.025 . The dihedral angle between the two planes is only 0.368.

No abstract

No abstract

Aims/hypothesis A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagonlike peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals. MethodsThe targeting of 111 In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq 111 In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq 111 In-labelled exendin in five patients with type 1 Maarten Brom and Wietske Woliner-van der Weg contributed equally to this study. Diabetologia (2014) 57:950-959 DOI 10.1007 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images. Results In rats, 111 In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes. Conclusions/interpretation These studies indicate that 111 Inlabelled exendin may be suitable for non-invasive quantification of BCM.