Effect of charge on in vitro and in vivo characteristics of radiolabeled DOTA-alpha-MSH analogues

摘要

As both melanotic and amelanotic melanomas overexpress receptors for alpha-melanocyte-stimulating hormone(melanocortin-1 receptor,MC1R),radiolabeled alpha-MSH analogues are potential candidates for melanoma diagnosis and therapy.Recently,the preparation and in vivo application of MSH octapeptides suitable for diagnosis(PET imaging,y-camera scintigraphy)of melanoma metastases has been reported.Although these derivatives displayed very favourable tumour-to-kidney ratios,MC1R-mediated internal radiotherapy of melanoma tumours using alpha-,beta-or Auger-electron emitters requires an even higher tumour specificity of the radiopeptides in order to avoid kidney damage.Therefore,we undertook a study with MSH octapeptides examining the role of the position of the metal chelator DOTA(l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid)at the N-terminus or at the Lys side-chain,as well as the effect of a free or blocked Lys~(11)epsilon-amino group,on the in vitro binding activity and in vivo tissue distribution of the radiopeptides.Here we present the in vitro data obtained with five different MSH octapeptides,of which the three containing the DOTA chelator were also labelled with in and studied in vivo.