%0 Journal Article
%T Blood-brain barrier transport kinetics of NOTA-modified proteins: the somatropin case.
%A Bracke N
%A Janssens Y
%A Wynendaele E
%A Tack L
%A Maes A
%A van de Wiele C
%A Sathekge M
%A de Spiegeleer B
%J Q J Nucl Med Mol Imaging
%V 64
%N 1
%D Mar 2020
%M 29697217
%F 1.56
%R 10.23736/S1824-4785.18.03025-X
%X <B>BACKGROUND: </B>Chemical modifications such as PEG, polyamine and radiolabeling on proteins can alter their pharmacokinetic behavior and their blood-brain barrier (BBB) transport characteristics. NOTA, i.e. 1,4,7-triazacyclononane-1,4,7-triacetic acid, is a bifunctional chelating agent that has attracted the interest of the scientific community for its high complexation constant with metals like gallium. Until now, the comparative BBB transport characteristics of NOTA-modified proteins versus unmodified proteins are not yet described.<BR><B>METHODS: </B>Somatropin (i.e. recombinant human growth hormone), NOTA-conjugated somatropin and gallium-labelled NOTA-conjugated somatropin were investigated for their brain penetration characteristics (multiple time regression and capillary depletion [CD]) in an in vivo mice model to determine the blood-brain transfer properties.<BR><B>RESULTS: </B>The three compounds showed comparable initial brain influx, with Kin=0.38±0.14 µL/(g×min), 0.36±0.16 µL/(g×min) and 0.28±0.18 µL/(g×min), respectively. CD indicated that more than 80% of the influxed compounds reached the brain parenchyma. All three compounds were in vivo stable in serum and brain during the time frame of the experiments.<BR><B>CONCLUSIONS: </B>Our results show that modification of NOTA as well as gallium chelation onto proteins, in casu somatropin, does not lead to a significantly changed pharmacokinetic profile at the blood-brain barrier.