Mario Fabiilli, Abstract Co-Author: Nothing to Disclose

Morand R. Piert MD, PhD, Abstract Co-Author: Nothing to Disclose

J. Brian Fowlkes PhD, Abstract Co-Author: Research support, General Electric Company Equipment support, General Electric Company Equipment support, Toshiba Corporation Research collaboration, Sonetics Inc Stockholder, HistoSonics, Inc Founder, HistoSonics, Inc

Paul L. Carson PhD, Abstract Co-Author: Research collaboration, General Electric Company Research collaboration, Sonetics Inc Research collaboration, ZONARE Medical Systems, Inc Research collaboration, Light Age, Inc

Xia Shao PhD, Abstract Co-Author: Nothing to Disclose

Oliver D. Kripfgans, Presenter: Research support, General Electric Company Equipment support, General Electric Company

Colloidal systems allow targeted delivery of drugs with a narrow therapeutic window, thereby minimizing systemic toxicity. Ultrasound (US) provides spatially and temporally controlled drug release and real-time therapy guidance. Positron emission tomography (PET) enables pharmacokinetic imaging of radiolabeled therapeutic agents for efficacy feedback and treatment planning.

Double emulsions containing fluorodeoxyglucose (18F, FDG) and perfluoropentane (PFP) were made using a double sonication approach. Previous studies on PFP droplets demonstrated transcutaneous therapy for vascular occlusion of the kidney and for drug delivery. The emulsion was administered IV to Fisher 344 rats with VEGF positive glioma tumors (9L) located on the upper forearm. Tumors were imaged pre-treatment using a clinical US scanner, operating a mechanically swept linear US array (L9/10L, GE, Milwaukee, WI), while the animal was in a fixed prone position.  Post emulsion-administration, the rats were imaged from mid abdomen to the brain, for 60 min using dynamic PET scans. Image registration of US and PET derived scan volumes was used to find drug distribution in context with anatomical features.

Size measurements of double emulsions yielded an average diameter of 1.9 μm with 99.5% < 8 μm. The emulsions, containing 5 μCi/mL, were administered at a PFP level of 0.12 g/kg. Biodistribution results showed minimal lung loading with a peak ROI level of 0.2% and a residual value of 0.15% after 60 min. Liver ROI levels peaked ~2 min post injection (PI) at 2.2%ID/g (injected dose/g) and leveled off at 1.25%ID/g ~15 min PI, suggesting particle clearance via the RE system. Tumor levels (0.35%ID/g) indicated FDG retention in the emulsion.

A double emulsion enables the incorporation of radiolabeled compounds for an US-mediated drug delivery system with multimodality imaging potential. Minimal pulmonary retention demonstrates the systemic circulation from an IV injection. Localization of drug delivery should be potentiated by focused US application. This system should allow feedback on tissue and cell targeted therapy, as well as localization and efficacy monitoring. (NIH grant 5R01EB000281)

Transcutaneous US has shown therapeutic effects; combination with PET will allow drug pathway imaging of delivery agents as well as their pharmacokinetics for real-time therapy feedback and planning.

Fabiilli, M, Piert, M, Fowlkes, J, Carson, P, Shao, X, Kripfgans, O, Ultrasound-activated Drug Delivery with PET-based Pharmacokinetics.  Radiological Society of North America 2010 Scientific Assembly and Annual Meeting, November 28 - December 3, 2010 ,Chicago IL. http://archive.rsna.org/2010/9013356.html