Chelating agents with lipophilic carriers
View Patent ↗Compounds useful for associating with nanoparticle or microparticle emulsions to obtain magnetic resonance images permit control of the relaxivity of the signal and readily associate with the particulate components.
1. A compound of the formula:
wherein Ch represents a chelating moiety comprising at least two nitrogens spaced by alkylene groups and to which carboxylic acid-bearing moieties are coupled;
m is 0-3;
each R 1 is independently a non-interfering substituent selected from the group consisting of halo, OR, NR 2 , SR, CN, NO 2 , SO 3 H, and R where R is alkyl or alkenyl optionally substituted by halo, or ═O, and optionally containing a heteroatom, such as O, S or N;
l is 0-2;
Z is S or O;
R 2 is H or alkyl (1-4C);
n is 1; and
each R 3 is independently an optionally substituted saturated or unsaturated hydrocarbyl group containing at least 10C, and
spacer is —CH 2 CH 2 — and/or includes a peptide, a pseudopeptide, or a polyalkylene glycol, optionally containing a cleavage site.
2. The compound of claim 1 , wherein the spacer is CH 2 CH 2 and R 2 is H.
3. The compound of claim 1 , wherein Z is S.
4. The compound of claim 1 , wherein R 2 is H.
5. The compound of claim 1 , wherein 1 is 0 and m is 1 or 0.
6. The compound of claim 1 , wherein each R 3 COO is a residue of a naturally occurring fatty acid or a mixture of said residues.
7. The compound of claim 1 , wherein R 1 is CH 3 O.
8. The compound of claim 1 , wherein the spacer is a peptide or a polyalkylene glycol.
9. The compound of claim 1 , which further comprises, associated with Ch, a paramagnetic metal ion or a radionuclide metal.
10. A composition which comprises the compound of claim 1 associated with lipophilic nanoparticles or microparticles.
11. A composition which comprises the compound of claim 9 associated with lipophilic nanoparticles or microparticles.
12. The composition of claim 10 , wherein said particles contain at least 2,000 copies of the compound of claim 1 .
13. The composition of claim 11 , wherein said particles contain at least 2,000 copies of the compound of claim 9 .
14. The composition of claim 10 , wherein the nanoparticles or microparticles further contain a targeting agent.
15. The composition of claim 11 , wherein the nanoparticles or microparticles further contain a targeting agent.
16. The composition of claim 14 , wherein said targeting agent is a receptor ligand or an antibody or fragment thereof.
17. The composition of claim 15 , wherein said targeting agent is a receptor ligand or an antibody or fragment thereof.
18. The composition of claim 10 , wherein said microparticles or nanoparticles further comprise a biologically active agent.
19. The composition of claim 11 , wherein said microparticles or nanoparticles further comprise a biologically active agent.
20. The composition of claim 10 , wherein said microparticles or nanoparticles are liposomes, oil droplets, perfluorocarbon nanoparticles, lipid-coated protein particles, or lipid-coated polysaccharides.
21. The composition of claim 11 , wherein said microparticles or nanoparticles are liposomes, oil droplets, perfluorocarbon nanoparticles, lipid-coated protein particles, or lipid-coated polysaccharides.
22. A method to obtain a magnetic resonance image or an image produced by a radionuclide which method comprises imaging a tissue which is associated with the composition of claim 11 .