The impact of weakly bound 89Zr on preclinical studies: Non-specific accumulation in solid tumors and aspergillus infection

Preclinical studies involving 89Zr often report significant bone accumulation, which is associated with dissociation of the radiometal from the tracer. However, experiments determining the uptake of unbound 89Zr in disease models are not performed as routine controls. The purpose of the present study was to investigate the impact of free or weakly bound 89Zr on PET quantifications in disease models, in order to determine if such control experiments are warranted.MethodsChemical studies were carried out to find a 89Zr compound that would solubilize the 89Zr as a weak chelate, thus mimicking free or weakly bound 89Zr released in circulation. 89Zr oxalate had the desired characteristics, and was injected into mice bearing FaDu and HT29 solid tumor xenografts, and mice infected in the lungs with the mold Aspergillus fumigatus, as well as in healthy controls (naïve). PET/CT or PET/MR imaging followed to quantify the distribution of the radionuclide in the disease models.Results89Zr oxalate was found to have a plasma half-life of 5.1 ± 2.3 h, accumulating mainly in the bones of all animals. Both tumor types accumulated 89Zr on the order of 2‐4 %ID/cm3, which is comparable to EPR-mediated accumulation of certain species. In the aspergillosis model, the concentration of 89Zr in lung tissue of the naïve animals was 6.0 ± 1.1 %ID/g. This was significantly different from that of the animals with advanced disease, showing 11.6 ± 1.8 %ID/g.ConclusionsGiven the high levels of 89Zr accumulation in the disease sites in the present study, we recommend control experiments mapping the biodistribution of free 89Zr in any preclinical study employing 89Zr where bone uptake is observed. Aqueous 89Zr oxalate appears to be a suitable compound for such studies. This is especially relevant in studies where the tracer accumulation is based upon passive targeting, such as EPR.