Dynamic imaging of arginine-rich heart-targeted vehicles in a mouse model.
Efficacious delivery of drugs and genes to the heart is an important goal. Here, a radiolabeled peptide-targeted liposome was engineered to bind to the heart, and the biodistribution and pharmacokinetics were determined by dynamic positron emission tomography in the FVB mouse. Efficient targeting occurred only with an exposed ligand and a dense concentration of peptide (6000 peptides/particles). Liposomes targeted with CRPPR or other arginine-rich peptides with an exposed guanidine moiety bound within 100 s after intravenous injection and remained stably bound. With CRPPR-targeted particles, the radioisotope density in the heart averaged 44 +/- 9% injected dose/gram of tissue, more than 30-fold higher than in skeletal muscle. The rapid and efficient targeting of these particles can be exploited in drug and gene delivery systems and with dynamic positron emission tomography provides a model system to optimize targeting of engineered particles.
Zhang
Hua
H
Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
Kusunose
Jiro
J
Kheirolomoom
Azadeh
A
Seo
Jai W
JW
Qi
Jinyi
J
Watson
Katherine D
KD
Lindfors
Heather A
HA
Ruoslahti
Erkki
E
Sutcliffe
Julie L
JL
Ferrara
Katherine W
KW
D000818:Animals; D001120:Arginine / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging*; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D005462:Fluorine Radioisotopes; D014677:Pharmaceutical Vehicles; D019275:Radiopharmaceuticals; D001120:Arginine