Agata A. Exner PhD, Presenter: Nothing to Disclose

Tianyi M. Krupka BS, Abstract Co-Author: Nothing to Disclose

Onkar S. Dhande, Abstract Co-Author: Nothing to Disclose

Nicholas T. Stowe PhD, Abstract Co-Author: Nothing to Disclose

John Robert Haaga MD, Abstract Co-Author: Nothing to Disclose

To demonstrate the potential of CT-guided, site-specific drug delivery, and establish a method for quantitative analysis of local drug release from polymer matrixes. The technique uses CT to directly visualize the IM injection of a PLGA polymer/carboplatin (platinum-containing drug) formulation, and uses the linear relationship between X-ray attenuation and Pt concentration to measure drug release noninvasively.

Male rats were anesthetized and 0.1ml of carboplatin suspension (mean dose 14”g/g) in dissolved PLGA was injected bilaterally into thigh muscle. After injection, a CT scan was performed (Philips Mx8000IDT, 120 kV, 410 mAs, and 0.8 mm slices) and was repeated at 24,48 or 168 hrs. Images were analyzed to establish appearance of the device, measure grayscale HU at t=0 and decrease in HU with time. Four implants were analyzed at 24 and 48 hrs, and two at 168 hrs. Percent of drug release was calculated and correlated with in vitro dissolution data. All data reported as mean±SE.

Upon contact with water, the polymer precipitated into a solid implant, and the drug diffused out of the matrix. Carboplatin in the implants was visible at t=0, with gray levels of 806±229 HU, well above that of muscle. CT measurement of drug release showed that 27±2,65±7 and 76±5% of drug was released at 24,48 and 168 hours. Implants analyzed in vitro showed an expedited release of 56±14,77±17 and 92±5% at the same times. Carboplatin released at 1.6%/hr in vitro and 1.4%/hr in vivo in the first 48 hrs and 0.09%/hr and 0.12%/hr at 48-168 hrs. Linear regression correlation showed an RČ of 0.96.

This ongoing study uses CT to guide and quantify the site-specific delivery of an injectable drug-loaded polymer. The analysis is straightforward and utilizes standard workstation software to calculate the change in HU in the implants with time. Results demonstrate method feasibility and validate the image data with a standard in vitro dissolution study. Importantly, the technique can be applied to various drug delivery systems, including intratumoral chemotherapy, to improve placement accuracy and provide essential in vivo data that typically cannot be obtained noninvasively.

Exner, A, Krupka, T, Dhande, O, Stowe, N, Haaga, J, Quantitative CT Imaging of Site-specific Drug Delivery.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4417177.html