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In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement

Sasha M. Demos, PhD^*, Hayat Alkan-Onyuksel, PhD^* , Bonnie J. Kane, BS, Kishin Ramani, MD, Ashwin Nagaraj, PhD, Rodney Greene, BS, Melvin Klegerman, PhD and David D. McPherson, MD

^* Department of Bioengineering, University of Illinois/Chicago, Chicago, Illinois, USA
Department of Pharmaceutics and Pharmacodynamics, University of Illinois/Chicago, Chicago, Illinois, USA
Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, Illinois, USA

View larger version (68K): [in a new window]   Figure 1 This figure illustrates liposomes suspended in a glass vial prior to (left) and after (right) the videodensitometry program to assess apparent brightness (see text for details).

View larger version (71K): [in a new window]   Figure 2 Intravascular ultrasound images of the right femoral artery of a Yucatan miniswine with a large central thrombus. (A) After injection of saline. (B) After injection of unconjugated liposomes. (C) After injection of antifibrinogen-labeled liposomes. (The dark central area is catheter imaging artifact. C = intraluminal thrombus/clot; arrows point to liposomes attached to thrombus.)

View larger version (131K): [in a new window]   Figure 3 Transvascular ultrasound images of an atherosclerotic left carotid artery of a Yucatan miniswine. (A) After injection of saline. (B) After injection of antifibrinogen-labeled liposomes (arrows point to liposomal attachment to fibrinogen in the atherosclerotic plaque).

View larger version (63K): [in a new window]   Figure 4 Similar to Figure 2, this illustrates intravascular ultrasound images of the atherosclerotic left carotid artery of a Yucatan miniswine (notice the circular atheroma deposition). (A) After injection of saline (arrows point to early atheroma). (B) After injection of unconjugated liposomes (arrows point to liposomes within the lumen). (C) After injection of anti–ICAM-1 labeled liposomes (arrows point to liposomes attached to the atherosclerotic plaque).

View larger version (90K): [in a new window]   Figure 5 Similar to Figure 3, this illustrates transvascular ultrasound images of the atherosclerotic left carotid artery of a Yucatan miniswine. (A) After injection of saline. (B) After injection of unconjugated liposomes (arrows point to liposomes within the lumen). (C) After injection of anti–ICAM-1 labeled liposomes (arrows point to liposomes attached to the atherosclerotic plaque).

View larger version (63K): [in a new window]   Figure 6 Gray scale values of antibody-conjugated liposomes (Conj Lip), unconjugated liposomes (Unconj Lip), agitated saline and blood during intravascular ultrasound imaging. The liposomes are brighter than saline and blood as determined by analysis of variance (p < 0.05).

View larger version (52K): [in a new window]   Figure 7 Gray scale values of antibody-conjugated liposomes (Conj Lip), unconjugated liposomes (Unconj Lip), agitated saline and blood during transvascular ultrasound imaging. Again the liposomes are brighter than saline and blood as determined by analysis of variance (p < 0.05).