Multimodal imaging method using nano-emulsion comprising optical nano-particles and perfluorocarbons

• US 8,753,606 B2
• Filed: 06/19/2009
• Issued: 06/17/2014
• Est. Priority Date: 06/21/2008
• Status: Active Grant

• Current Assignee: Korea Research Institute of Bioscience & Biotechnology
• Original Assignee: Korea Research Institute of Bioscience & Biotechnology
• Inventors: Chung, Bong Hyun, Lim, Yong Taik
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): PERREIRA, MELISSA JEAN
• Application Number:
  US13/000,197
• Publication Number:
  US 20110110867A1
• Time in Patent Office: 1,824 Days
• Field of Search: 424/9.1
• US Class Current: 424/9.1
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0017 Fluorescence in vivo
• CPC Class Codes: A61K 49/0067 quantum dots, fluorescent nanocrystals
• CPC Class Codes: A61K 49/0078 microemulsion, nanoemulsion
• CPC Class Codes: A61K 49/1806 Suspensions, emulsions, colloids, dispersions

Abstract

The present invention relates to a multimodal imaging method using a nano-emulsion comprising optical nano-particles and perfluorocarbons, and more particularly, to a method of obtaining multimodal images using a nano-emulsion consisted of perfluorocarbons for multispectral magnetic resonance imaging (MRI) and nano-particles for multicolor fluorescent detection. In the multimodal imaging method, various multispectral MRI images and multicolor fluorescent rays can be obtained by varying the kind and combination of perfluorocarbons and the kind and combination of optical nano-particles, so that multiplexed analysis is possible. Accordingly, the multimodal imaging method can be applied to various fields, including biological and medical fields in which studies on cell molecular imaging has been conducted.

Claims

1. A multimodal imaging method in vivo using a nano-emulsion comprising quantum dot nano-particles reformed with a perfluorocarbon for surface reforming, and ¹⁹F-containing perfluorocarbons, the method comprising:

injecting the nano-emulsion in vivo to simultaneously perform multicolor ray emission of the quantum dot nano-particles and control of resonance frequencies in accordance with the kinds of ¹⁹F-containing perfluorocarbons (a first step);

measuring the combined wavelength of the emitted rays and the controlled resonance frequency of the ¹⁹F-containing perfluorocarbons (a second step);

wherein the quantum dot nano-particles reformed with a perfluorocarbon for surface reforming are dispersed in the ¹⁹F-containing perfluorocarbons; and

the perfluorocarbon for surface reforming is not a ¹⁹F-containing perfluorocarbon.

2. The method according to claim 1, wherein m×

n multimodal images can be simultaneously obtained using combinations of multispectral MRI images and multicolor fluorescent rays, which obtained by combinations of the number (m) of kinds of the perfluorocarbons and the number (n) of the multicolor fluorescent rays generated from quantum dot nano-particles.

3. The method according to claim 1, wherein the quantum dot nano-particles has a structure in the form of a single core or core/shell and comprises compounds containing two or more elements from Group II-VI or III-V in the periodic table.

4. The method according to claim 1, wherein the ¹⁹F-containing perfluorocarbon containing the reformed quantum dot nano-particle is encapsulated in a lipid liposome.

5. The method according to claim 1, wherein the perfluorocarbon for surface reforming includes perfluorochemical having one end group selected from the group consisting of thiol, phosphine and phosphine oxide, or amphiphilic fluorinated hydrocarbon.

6. The method according to claim 1, wherein the perfluorocarbon for surface reforming includes one selected from the group consisting of perfluorinated alcohol phosphate ester and its salt, perfluorinated sulfonamide alcohol phosphate ester and its salt, perfluorinated alkyl sulfonamide alkylene quaternary ammonium salt, N,N-(carboxyl-substituted lower alkyl) perfluorinated alkyl sulfonamide, and a compound thereof.

7. The method according to claim 6, wherein the perfluorinated alcohol phosphate ester includes a free acid of mono or bis(1H,1H,2H,2H-perfluoroalkyl)phosphate derived diethanolamine salt.

8. The method according to claim 6, wherein the perfluorinated sulfonamide alcohol phosphate ester is one selected from the group consisting of perfluoro-n-octyl-N-ethysulfonamidoethyl phosphate, bis(perfluoro-n-octyl-N-ethylsulfonamidoethyl)phosphate, ammonium salt of bis(perfluoro-n-octyl-N-ethylsulfonamidoethyl)phosphate, bis(perfluorodecyl-N-ethylsulfonamidoethyl phosphate and bis(perfluorohexy-N-ethylsulfonamidoethyl)phosphate.

9. The method according to claim 2, wherein the multispectral magnetic resonance images are obtained by a ¹⁹F-containing perfluorocarbon or its derivative.

10. The method according to claim 9, wherein the ¹⁹F-containing perfluorocarbon includes at least one functional group connected to a main chain consisting of carbon atoms.

11. The method according to claim 9, wherein the ¹⁹F-containing perfluorocarbon is one selected from the group consisting of perfluorotributylamine (FC47), perfluorodecalin (PP5), perfluoromethyldecalin (PP9), perfluorooctylbromide, perfluorotetrahydrofuran (FC80), perfluoroether (PID) [(CF₃)₂CFOCF₂(CF₂)₂CF₂OCF(CF₃)₂], perfluoroether (PIID) [(CF)₂CFOCF₂(CF₂)₆CF₂OCF(CF₃)₂], perfluoroetherpolymer (Fomblin Y/01), perfluorododecane, perfluorobicyclo[4.3.0]nonane, perfluorotritrimethylbicyclohexane, perfluorotripropylamine, perfluoroisopropylcylcohexane, perfluomendotetrahydrodicyclopentodiene, perfluoroadamantane, perfluoroexotetrahydrodicyclopentadiene, perfluorobicyclo[5.3.0]decane, perfluorotetramethylcyclohexane, perfluoro-1-methyl-4-isopropylcyclohexane, perfluoro-n-butylcyclohexane, perfluorodimethylbicyclo[3.3.1]nonane, perfluoro-1-methyl-4-t-butylcyclohexene, perfluorodecahydroacenapthene, perfluoro-nundecane, perfluorotetradecahydrophenanthrene, perfluoro-1,3,5,7-tetramethyladamantane, perfluorododecahydrofluorene, perfluoro-1-3-dimethyladamantane, perfluoro-n-octylcyclohexane, perfluoro-7-methyl bicyclo[4.3.0]nonane, perfluoro-p-diisopropylcyclohexane, perfluoro-m-diisopropylcyclohexane, perfluoro-4-methyloctahydroquinolidizine, perfluoro-N-methyldecahydroquinoline, F-methyl-1-oxadecalin, perfluorooctahydroquinolidizine, perfluoro 5,6-dihydro-5-decene, perfluoro-4,5-dihydro-4-octene, perfluorodichlorooctane, perfluorobischlorobutyl ether, perfluorooctane, perfluorodichlorooctane, perfluoro-n-octylbromide, perfluoroheptane, perfluorodecane, perfluorocyclohexane, perfluoromorpholine, perfluorotripropylamine, perfluorotributylamine, perfluorodimethylcyclohexane, perfluorotrimethylcyclohexane, perfluorodicyclohexylether, perfluoro-n-butyltetrahydrofuran, perfluoro-15-crown-5ether and compounds structurally similar thereto.