Elizabeth J. Sutton MD, Presenter: Nothing to Disclose

Sidhartha Tavri MBBS, Abstract Co-Author: Nothing to Disclose

Tobias D. Henning MD, Abstract Co-Author: Nothing to Disclose

Louis Chesler MD, PhD, Abstract Co-Author: Nothing to Disclose

Daryl C. Drummond PhD, Abstract Co-Author: Nothing to Disclose

Heike E. Daldrup-Link MD, PhD, Abstract Co-Author: Nothing to Disclose

To develop a liposome co-encapsulated with a near-infrared (NIR) dye and doxorubicin and to image its integration in ovarian tumors with optical imaging (OI).

Minimally pegylated liposomes (LS, size: 100nm) were loaded with a water-soluble NIR dye (ADS645WS, ex/em: 641/661nm) and doxorubicin. The agent was purified by gel filtration. Probe sensitivity and stability was evaluated by spectrometry and fluorescence microscopy. The fluorescence of increasing concentrations was evaluated in vitro. 5x106 IGROV-1 cells were implanted subcutaneously into 9 athymic nude rats. ADS645WS-Doxorubicin-Ls (6.7µm PL/kg and 5mg Dox/kg) was injected intravenously when the tumors were 5mm2. OI were acquired pre, 1, 4, 8, 24, 48 and 72 hours post-injection (p.i.). Regions-of-interest were defined as 50% of maximum signal intensity. Results were correlated with histopathology and compared with a t-test for statistical significance.

Doxorubicin-ADS645WS-LS showed a strong fluorescence, which increased with concentration (p<0.05). n=6 rats demonstrated a significantly increased fluorescence of the ovarian tumor after Doxorubicin-ADS645WS-LS injection compared to precontrast scans (p<0.05), which peaked at 8 hours p.i. Variable OI tumor enhancement correlated directly with tumor vascularity on histopathology (p<0.05). Tumors with extensive central necrosis (n=3) did not fluoresce (p>0.05), while vascular tumors showed significant fluorescence p.i. of Doxorubicin-ADS645WS-LS (p<0.05). The distribution of the fluorescent dye within the tumor was confirmed by fluorescence microscopy.

Doxorubicin-ADS645WS-LS accumulation within vascular ovarian tumors can be monitored in vivo with OI. Further studies are currently pursued to explore co-encapsulation effects, pharmacokinetics and in vivo drug release rates.

OI can facilitate chemotherapeutic monitoring and dose optimization and thus can potentially accelerate the development process and allow for targeted individualized therapy.

Sutton, E, Tavri, S, Henning, T, Chesler, L, Drummond, D, Daldrup-Link, H, To Develop a Liposome Coencapsulated with a Near Infrared (NIR) Dye and Doxorubicin and to Image Its Integration in Ovarian Tumors with Optical Imaging (OI).  Radiological Society of North America 2009 Scientific Assembly and Annual Meeting, November 29 - December 4, 2009 ,Chicago IL. http://archive.rsna.org/2009/8013340.html