title: In vivo distribution of liposome-encapsulated hemoglobin determined by positron emission tomography.
abstract: Positron emission tomography (PET) is a noninvasive imaging technology that enables the determination of biodistribution of positron emitter-labeled compounds. Lipidic nanoparticles are useful for drug delivery system (DDS), including the artificial oxygen carriers. However, there has been no appropriate method to label preformulated DDS drugs by positron emitters. We have developed a rapid and efficient labeling method for lipid nanoparticles and applied it to determine the movement of liposome-encapsulated hemoglobin (LEH). Distribution of LEH in the rat brain under ischemia was examined by a small animal PET with an enhanced resolution. While the blood flow was almost absent in the ischemic region observed by [(15)O]H(2)O imaging, distribution of (18)F-labeled LEH in the region was gradually increased during 60-min dynamic PET scanning. The results suggest that LEH deliver oxygen even into the ischemic brain from the periphery toward the core of ischemia. The real-time observation of flow pattern, deposition, and excretion of LEH in the ischemic rodent brain was possible by the new methods of positron emitter labeling and PET system with a high resolution.
authors.affiliation: Department of Medical Biochemistry and Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Urakami
authors.forename: Akira T
authors.initials: AT
authors.lastname: Kawaguchi
authors.forename: Shuji
authors.initials: S
authors.lastname: Akai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hatanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koide
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Dai
authors.initials: D
authors.lastname: Fukumoto
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002545:Brain Ischemia / Q000000981:diagnostic imaging*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods; D008081:Liposomes; D008297:Male; D049268:Positron-Emission Tomography / Q000191:economics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001802:Blood Substitutes; D005462:Fluorine Radioisotopes; D008081:Liposomes