Traditional means to identify the physiological severity of arterial disease are hampered by their inability to identify atheroma extent and composition. New techniques that identify atheroma in vivo are being developed, however, accurate methodologies for atheroma characterization are hampered, due to the heterogeneous nature of the disease process. Novel acoustic targeting and highlighting agents, such as liposomes, may overcome these problems. Liposomes are phospholipid vesicles enclosing an aqueous space. We have developed a unique methodology that, by process and composition, provides acoustic characteristics of liposomes. This formulation allows modification for antibody conjugation and therapeutic drug incorporation. Preliminary work by this group has been centered on the optimization of formulation, optimization of conjugation, and development of in vitro and in vivo quantitation techniques. This proposal describes a series of protocols to optimize highlighting and enhancing We plan to investigate the potential of these formulations to aid other imaging modalities as atheroma enhancement agents. Our long term goals are to determine, quantitate, and characterize the stage, extent, and physiologic severity of atherosclerosis and allow directed therapy to improve physiologic flow following intervention.

Public Health Relevance

This proposal seeks to develop a stable formulation (echogenic immunoliposomes) that has the ability to highlight, characterize, and quantify the progression of atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059586-11
Application #
8265981
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Danthi, Narasimhan
Project Start
1998-06-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
11
Fiscal Year
2012
Total Cost
$426,361
Indirect Cost
$98,747
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Klegerman, Melvin E; Naji, Ali K; Haworth, Kevin J et al. (2016) Ultrasound-enhanced bevacizumab release from echogenic liposomes for inhibition of atheroma progression. J Liposome Res 26:47-56
Haworth, Kevin J; Salgaonkar, Vasant A; Corregan, Nicholas M et al. (2015) Using passive cavitation images to classify high-intensity focused ultrasound lesions. Ultrasound Med Biol 41:2420-34
Raymond, Jason L; Luan, Ying; van Rooij, Tom et al. (2015) Impulse response method for characterization of echogenic liposomes. J Acoust Soc Am 137:1693-703
Radhakrishnan, Kirthi; Haworth, Kevin J; Peng, Tao et al. (2015) Loss of echogenicity and onset of cavitation from echogenic liposomes: pulse repetition frequency independence. Ultrasound Med Biol 41:208-21
Kim, Hyunggun; Kee, Patrick H; Rim, Yonghoon et al. (2015) Nitric Oxide-Enhanced Molecular Imaging of Atheroma using Vascular Cellular Adhesion Molecule 1-Targeted Echogenic Immunoliposomes. Ultrasound Med Biol 41:1701-10
Klegerman, Melvin E; Zou, Yuejiao; Golunski, Eva et al. (2014) Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity. J Liposome Res 24:216-22
Raymond, Jason L; Haworth, Kevin J; Bader, Kenneth B et al. (2014) Broadband attenuation measurements of phospholipid-shelled ultrasound contrast agents. Ultrasound Med Biol 40:410-21
Kim, Hyunggun; Britton, George L; Peng, Tao et al. (2014) Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage. Int J Nanomedicine 9:155-65
Kee, Patrick H; Kim, Hyunggun; Huang, Shaoling et al. (2014) Nitric oxide pretreatment enhances atheroma component highlighting in vivo with intercellular adhesion molecule-1-targeted echogenic liposomes. Ultrasound Med Biol 40:1167-76
Gruber, Matthew J; Bader, Kenneth B; Holland, Christy K (2014) Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound. J Acoust Soc Am 135:646-53

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