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In vitro and in vivo evaluation of selected 68Ga-siderophores for infection imaging

M. Petřík,H. Haas,Markus Schrettl,A. Helbok,M. Blatzer,C. Decristoforo

Published 2012 in Nuclear Medicine and Biology

ABSTRACT

Introduction Siderophores are low-molecular-mass iron chelators serving as iron transporters for almost all bacteria, fungi and some plants. Iron is an essential element for majority of organisms and plays an important role in virulence of pathogenic organisms. 68Ga is a positron emitter with complexing properties comparable to those of Fe(III) and readily available from a generator. Initial studies with 68Ga-triacetylfusarinine C (TAFC) showed excellent targeting properties in a rat infection model. We report here on the in vitro and in vivo evaluation of other siderophores radiolabelled with 68Ga as potential radiopharmaceuticals for infection imaging. Methods 68Ga labelling was performed using acetate buffer. Stability, log P and protein binding values were determined. In vitro uptake was tested using iron-deficient and iron-sufficient Aspergillus fumigatus (A.f.) cultures. Biodistribution of 68Ga-siderophores was studied in Balb/c mice. Results Significant differences among studied siderophores were observed in labelling efficiency, stability and protein binding. Uptake in A.f. cultures was highly dependent on iron load and type of the siderophore. In mice, 68Ga-TAFC and 68Ga-ferrioxamine E (FOXE) showed rapid renal excretion and low blood values even at a short period after injection; in contrast, 68Ga-ferricrocin and 68Ga-ferrichrome revealed high retention in blood and 68Ga-fusarinine C showed very high kidney retention. Conclusions Some of the studied siderophores bind 68Ga with high affinity and stability, especially 68Ga-TAFC and 68Ga-FOXE. Low values of protein binding, high and specific uptake in A.f., and excellent in vivo biodistribution make them favourable agents for Aspergillus infection imaging.

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