A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity.

ABSTRACT: We introduce a new category of nanoparticle-based T(1) MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd(3+)·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and ?-cyclodextrin (CD). A small library of Gd(3+)·DOTA-encapsulated supramolecular nanoparticles (Gd(3+)·DOTA?SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd(3+)·DOTA?SNP library. Consequently, an optimal synthetic formulation of Gd(3+)·DOTA?SNPs with an r(1) of 17.3 s(-1) mM(-1) (ca. 4-fold higher than clinical Gd(3+) chelated complexes at high field strengths) was identified. T(1)-weighted imaging of Gd(3+)·DOTA?SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd(3+)·DTPA. A Gd(3+)·DOTA?SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd(3+)·DOTA?SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T(1)-weighted imaging after injecting Gd(3+)·DOTA?SNPs but not after injecting Gd(3+)·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd(3+)·DOTA?SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis.

SUBMITTER: Chen KJ 

PROVIDER: S-EPMC3032383 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature