68Ga-TAFC for PET imaging of pulmonary aspergillosis, proof of principle

Objectives Pulmonary aspergillosis (PA) is a life threatening disease and diagnostic options are limited. Iron plays an essential role for the virulence of Aspergillus ssp (A.s.). A.s. employ specific and efficient iron transporter mechanisms based on iron complexing siderophores, which are upregulated during infection. We aimed to evaluate the potential of a peptide siderophore radiolabelled with ⁶⁸Ga.

Methods Triacetylfusarinine (TAFC) was chosen as model siderophore for ⁶⁸Ga labelling. Radiolabelling was performed at RT. Stability in solution and serum was determined. In vitro uptake in A.s. cultures was tested using varying iron load, blocking with excess siderophore and NaN₃. Biodistribution was studied in normal balb/c mice. Specific uptake was studied in a PA model in immunosupressed Sprague Dawley rats.

Results High S.A. labelling with quantitative yields could be achieved at RT. ⁶⁸Ga-TAFC was stable in serum, towards DTPA and Fe(III) challenge. Uptake in A.s. was highly efficient, specific, energy and iron dependent. ⁶⁸Ga-TAFC showed rapid renal excretion, low blood values and high metabolic stability. In the rat PA model, lung uptake (mean n=3) was <0.04%ID/g in control rats, 0.29% ±0.11 ID/g in mild and 0.82±0.31ID/g in severe infection. PET-imaging showed focal accumulation of ⁶⁸Ga-TAFC in infected lung tissue.

Conclusions This work proves the potential of using ⁶⁸Ga labelled peptide siderophores for specific infection detection. ⁶⁸Ga-TAFC holds promise as a new PET agent for imaging PA.