vasoactive-intestinal-peptide and 1-4-7-10-tetraazacyclododecane--1-4-7-10-tetraacetic-acid

Vasoactive intestinal peptide (VIP) receptors are overexpressed in a broad variety of tumours. For the detection of these tumours, novel chemically modified and shortened VIP derivatives were designed.. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-derivatised VIP analogues were radiolabelled with (111)In and in vitro and in vivo behaviour was evaluated using stability and internalisation assays, as well as an initial biodistribution study.. Radiolabelling of the VIP analogues resulted in high radiochemical yields, without need for further purification steps. Stability of the VIP derivatives was variable and cell uptake studies in VIP receptor-positive cell lines revealed that only a limited number of derivatives were internalised. In the tumour mouse model, no specific tumour targeting was shown.. Since the tested VIP derivatives exhibited impaired in vitro and in vivo characteristics alternative modifications to increase their stability while retaining receptor affinity should be considered to enable the use of synthetic VIP analogues for tumour targeting.

Topics: Animals; Binding, Competitive; Carcinoma, Pancreatic Ductal; Cells, Cultured; CHO Cells; Cricetinae; Drug Design; Female; Heterocyclic Compounds, 1-Ring; Humans; Indium Radioisotopes; Mice; Mice, Inbred BALB C; Mice, Nude; Pancreatic Neoplasms; Peptide Fragments; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Vasoactive Intestinal Peptide; Tissue Distribution; Vasoactive Intestinal Peptide