Assessment of the biodistribution of an [¹⁸F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

Abstract

Perfluorocarbon (PFC) double emulsions loaded with a water-soluble, therapeutic agent can be triggered by ultrasound in a process known as acoustic droplet vaporization (ADV). Elucidating the stability and biodistribution of these sonosensitive vehicles and encapsulated agents are critical in developing targeted drug delivery strategies using ultrasound. [18F]fluorodeoxyglucose (FDG) was encapsulated in a PFC double emulsion and the in vitro diffusion of FDG was assessed using a Franz diffusion cell. Using dynamic micro positron emission tomography (micro-PET) and direct tissue sampling, the biodistribution of FDG administered as a solution (i.e. non-emulsified) or as an emulsion was studied in Fisher 344 rats (n = 6) bearing subcutaneous 9L gliosarcoma. Standardized uptake values (SUVs) and area under the curve of the SUV (AUCSUV) of FDG were calculated for various tissues. The FDG flux from the emulsion decreased by up to a factor of 6.9 compared to the FDG solution. FDG uptake, calculated from the AUCSUV, decreased by 36% and 44% for brain and tumor, respectively, when comparing FDG solution versus FDG emulsion (p < 0.01). Decreases in AUCSUV in highly metabolic tissues such as brain and tumor demonstrated retention of FDG within the double emulsion. No statistically significant differences in lung AUCSUV were observed, suggesting minimal accumulation of the emulsion in the pulmonary capillary bed. The liver AUCSUV increased by 356% for the FDG emulsion, thus indicating significant hepatic retention of the emulsion.

Emulsion Techniques for the Production of Pharmacological Nanoparticles

“…PET is an attractive nuclear imaging technique based on the detection of photons arising from annihilation of electron (e − ) with a positron (e + ), emitted by PET radionuclide. PET can image deep tissue with high sensitivity (0.02–0.1 cps/Bq) and is widely used in preclinical and clinical imaging of diseases . PET offers non‐invasive quantification of biodistribution and concentration of probes labeled with radionuclides in a body and bloodstream such as determination of drug concentration in tissues as low as 10 −12 mol L −1 .…”

Acceleration of ultrasound thermal therapy by patterned acoustic droplet vaporization

“…In a highly perfused organ such as liver, with an average fractional blood volume of 31% (Schwickert et al, 2005), 3.23 Â 10 5 droplets/mL of blood are required for HIFU lesions in a 70 kg human with 5 L blood volume. Systemically, this yields 2.3 Â 10 7 droplets/kg, which is 282-times lower in concentration than a recent biodistribution study where a similar emulsion was safely tolerated at 6.5 Â 10 9 droplets/kg (Fabiilli et al, 2013).…”

“…However, UCAs also move the greatest heating position from the focus by up to 2 cm for a given transducer geometry and aberrating tissues intervening the acoustic path as well as create surface lesions for concentrations greater than 0.1% (v/v), with some damage well outside the lesion (Tung et al, 2006). Alternatively, acoustic droplet vaporization (ADV) is an ultrasound-based method of converting biocompatible microdroplets (Fabiilli et al, 2013) into microbubbles. When exposed to acoustic pressures above the vaporization threshold, injected perfluorocarbon microdroplets-which are similar in size to UCAs-produce microbubbles that are more than 100-fold larger in volume than the original microdroplets, resulting in a local increase in the acoustic absorption.…”

In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets

“…This strategy was also used by Fabiilli and co-workers to carry and release chlorambucil, a lipophilic chemotherapeutic [20], and thrombin, a serine protease used in the treatment of pseudoan-eurysms [21]. More recently, Fabiilli et al also reported the biodistribution of such composite droplets of perfluorocarbon (6 µm or less in diameter) in rats [22]. While this technology appeared very useful for internal tattooing of tissues, the slow leakage of the encapsulated compound observed from uninduced droplets appeared as a potential drawback to envision the adaptation of this concept to the delivery of highly toxic anticancer agents.…”