GDCC provides a prolonged blood pool retention time for effective MRI contrast enhancement and then clears rapidly with minimal accumulation of Gd (III) ions. It is promising for further development as a blood pool MRI contrast agent.
Both GDCP and GDCEP provided effective contrast enhancement for MR imaging of the blood pool. The accumulation of toxic Gd(III) ions in the body was greatly reduced with GDCP and GDCEP as compared to the nondegradable control.
Biomedical imaging is valuable for non-invasive investigation of in vivo drug delivery with polymer conjugates. It can provide real-time information on pharmacokinetics, biodistribution and drug delivery efficiency of the conjugates. Non-invasive visualization of in vivo drug delivery of polymer conjugates with contrast enhanced magnetic resonance imaging (MRI) was studied with paramagnetically labeled poly(L-glutamic acid) in an animal tumor model. Poly(L-glutamic acid) is a biocompatible and biodegradable drug carrier for diagnostics and therapeutics. Poly(L-glutamic acid)-1,6-hexanediamine-(Gd-DO3A) conjugates with molecular weights of 87, 50 and 28 KDa and narrow molecular weight distributions were prepared and studied in mice bearing MDA-MB-231 human breast cancer xenografts. Contrast enhanced MRI resulted in real-time and three-dimensional visualization of blood circulation, pharmacokinetics, biodistribution and tumor accumulation of the conjugates, and the size effect on these pharmaceutics properties. The conjugate of 28 KDa rapidly cleared from the circulation and had a relatively lower tumor accumulation. The conjugates with higher molecular weights exhibited a more prolonged blood circulation and higher tumor accumulation. The difference between the conjugates of 87 and 50 KDa was not significant. Contrast enhanced MRI is effective for non-invasive real-time visualization of in vivo drug delivery of paramagnetically labeled polymer conjugates.
Nanoconjugates composed of TiO 2 nanoparticles, DNA oligonucleotides and a gadolinium contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these nanoconjugates showed them to be superior to the free contrast agent of same formulation with regard to 1) intracellular accumulation, 2) retention and 3) subcellular localization. Our results have shown that 48 hours after treatment, the concentration of gadolinium in nanoconjugate treated cells was 1000 fold higher compared to cells treated with contrast agent alone. Consequently, T 1 -weighted contrast enhancements were observed in cells treated with nanoconjugates but not in cells treated by the contrast agent alone. This type of nanoconjugate with increased retention time, Gd accumulation and intracellular delivery may find its use in gadolinium neutron-capture cancer therapy.
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