Biodistribution of 89Zr-oxalate in tumor bearing mice

Objectives Preclinical PET studies employing 89Zr as the radiolabel often describe biodistributions with elevated bone uptake. This indicates a propensity for the zirconium to become ‘free’ from the intended tracer. Therefore it is important to determine the level of tumor accumulation of weakly bound 89Zr before assigning significance to targeted uptake. The objectives of this study were to: 1. Determine the extent of tumor accumulation of weakly chelated 89Zr in FaDu and HT29 preclinical models. 2. Provide a control experiment to other preclinical studies which observe non-specific accumulations (i.e. bone uptake) of 89Zr.

Methods Left and right flank tumors were established in NMRI nude mice by subcutaneous injection of either 10^6 FaDu or HT29 cells and were allowed to grow for 2-3 weeks (50-500 mm3). 89Zr was produced as the chloride as described by Holland (NMB 2009), dried, and taken up in 10mM sodium oxalate at pH 6.5 in isotonic saline. Three mice with FaDu xenografts, and four with HT29 xenografts had 9-15 MBq of this 89Zr activity (100 µl) injected and imaging was performed on a microPET 120 scanner, with 10 minute static scans followed by micro CT at 1, 6, 20, 45, and 68 hours post injection.

Results Both tumor types showed significant uptake, 2-4% ID/g, with tumor-to-muscle ratios ranging from 1.5-5 at all time points. The blood pool (heart ROI) cleared with a half-life of around 7 hours. Bone uptake was prominent, peaking at 15% ID/g at 45h.

Conclusions 89Zr injected as the oxalate is a long-circulating zirconium tracer that is useful for determining the biodistribution of weakly chelated zirconium in preclinical models. Tumor uptake of 89Zr was significant, between 2-4% ID/g. Given the high lesion accumulation of free 89Zr, care should be taken when assigning significance to PET data when bone uptake is observed.