Evaluating Radioactive Analogs of Doxorubicin to Quantify ChemoFilter Binding and Whole Body PET/MR Drug Biodistribution.

Evaluate radiolabeled doxorubicin (Dox) analogs as a tracers of baseline Dox biodistribution in vivo during hepatic intra-arterial chemotherapy and to assess efficacy of ChemoFilter devices to bind Dox in vitro.In vitro static experiment: N-Succinimidyl 4-fluorobenzoate ([18F]SFB) and [18F]FB-Dox were added to a beaker containing a filter material (Dowex resin, ssDNA resin, or sulfonated coated mesh). In vitro flow model: [18F]FB-Dox was added into Dox solution in PBS and the solution flowed via a syringe column containing the filter materials. In vitro flow experiment in micro-PET: Images were taken as [18F]SFB and [18F]FB-Dox moved through a phantom. In vivo biodistribution testing: A catheter was placed into the common hepatic artery of a swine. [18F]FB-Dox was infused over 30 seconds. A 10 minute dynamic image and three 20 minute static images were acquired utilizing a 3T PET/MRI.In vitro static experiment: [18F]FB-Dox demonstrated 76.7%, 88.0%, and 52.4% binding on Dowex resin, ssDNA resin, and coated mesh respectively. In vitro flow model: First pass binding of [18F]FB-Dox to Dowex, ssDNA, and coated mesh was 76.7%, 74.2%, and 76.2% and total bound was 80.9%, 84.6%, and 79.9% respectively. In vitro flow experiment in micro-PET: Phantom demonstrated a greater amount of [18F]FB-Dox bound to both filter cartridges compared to [18F]SFB. In vivo biodistribution testing: The first 10 minutes depicted [18F]FB-Dox moving through the right upper quadrant of the abdomen. ROI analysis showed the relative amount in the gallbladder increased by 2.97x and kidney by 1.08x. The amount decreased in the brain by 0.74x and heart by 0.57x.[18F]FB-Dox can be used to assess Dox binding to ChemoFilters and in vivo biodistribution. This sets the stage for evaluation of ChemoFilter efficacy in reducing the toxicity of intra-arterial chemotherapy.