High relaxivity trimetallic nitride (Gd3N) metallofullerene MRI contrast agents with optimized functionality.
Water-soluble poly(ethylene glycol) (PEG) functionalized and hydroxylated endohedral trimetallic nitride metallofullerene derivatives, Gd(3)N@C(80)[DiPEG(OH)(x)], have been synthesized and characterized. The (1)H MRI relaxivities in aqueous solution were measured for the derivatives with four different molecular weights of PEG (350-5000 Da) at 0.35, 2.4, and 9.4 T. The 350/750 Da PEG derivatives have the highest relaxivities among the derivatives, 237/232 mM(-1) s(-1) for r(1) and 460/398 mM(-1) s(-1) for r(2) (79/77 mM(-1) s(-1) and 153/133 mM(-1) s(-1) based on Gd(3+) ion), respectively, at a clinical-range magnetic field of 2.4 T. These represent some of the highest relaxivities reported for commercial or investigational MRI contrast agents. Dynamic light scattering results confirm a larger average size for 350/750 Da PEGs derivatives (95/96 nm) relative to longer chain length derivatives, 5000 Da PEG derivatives (37 nm). Direct infusion of the optimized 350 Da PEG derivatives into live tumor-bearing rat brains demonstrated an initial uniform distribution, and hence, the potential for effective brachytherapy applications when the encapsulated Gd(3+) ions are replaced with radioactive (177)Lu.
Zhang
Jianfei
J
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24060, USA.
Fatouros
Panos P
PP
Shu
Chunying
C
Reid
Jonathan
J
Owens
Lesley Shantell
LS
Cai
Ting
T
Gibson
Harry W
HW
Long
Gary L
GL
Corwin
Frank D
FD
Chen
Zhi-Jian
ZJ
Dorn
Harry C
HC
D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis*; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D037741:Fullerenes / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008958:Models, Molecular; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000175:diagnosis; D009584:Nitrogen / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D014018:Tissue Distribution
D003287:Contrast Media; D037741:Fullerenes; D009942:Organometallic Compounds; D011092:Polyethylene Glycols; D005682:Gadolinium; D009584:Nitrogen