Paramagnetic metals can induce T1 shortening by interaction with free water molecules. Two
metal ions,
Gadolinium and
Manganese, are currently available for human use.
Gadolinium-based MRI
contrast agents (CAs) can operate using a approximately 100-fold lower concentration of
Gadolinium ions in comparison to the necessary concentration of
Iodine atoms employed in CT imaging in the tissues. Therefore, numerous macromolecular MRI CAs prepared employing relatively simple chemistry are readily available that can provide sufficient enhancement for multiple applications. Herein, we describe the synthesis, characteristics, and potential applications of
dendrimer-based macromolecular MRI CAs in our recently reported libraries. This entire series of
dendrimer-based macromolecular MRI CAs have a spherical shape and possess similar surface charges. Changes in molecular size altered the route of excretion. Smaller sized
contrast agents, of less than 60 kD molecular weight, were excreted through the kidney resulting in these agents being potentially suitable as functional renal
contrast agents. Less hydrophilic and larger sized
contrast agents were found better suited for use as blood pool
contrast agents. Hydrophobic variants of CAs formed with
polypropylenimine diaminobutane
dendrimer cores quickly accumulated in the liver and can function as liver
contrast agents. Larger hydrophilic agents are also useful for lymphatic imaging. Finally,
contrast agents conjugated with either
monoclonal antibodies or with
avidin are able to function as
tumor-specific
contrast agents and might also be employed as therapeutic drugs for either
gadolinium neutron capture therapy or in conjunction with
radioimmunotherapy.