Dendrimer-based contrast agents for molecular imaging.

The extensive adaptability of dendrimer-based contrast agents is ideal for the molecular imaging of organs and other target-specific locations. The ability of literally atom-by-atom modification on cores, interiors, and surface groups, permits the rational manipulation of dendrimer-based agents in order to optimize their physical characteristics, biodistribution, receptor-mediated targeting, and controlled release of the payload. Such modifications enable agents to localize preferentially to areas or organs of interest for facilitating target-specific imaging as well as assume excretion pathways that do not interfere with desired applications. Recent innovations in dendrimer research have increased agent directibility and new synthetic chemistry approaches have increased efficiency of production as well as led to the creation of novel dendrimer-based contrast agents. In addition, by taking advantage of the numerous attachment sites available on the surface of a single dendrimer molecule, new synthetic chemistry techniques have led to the development of multi-modality magnetic resonance, radionuclide, and fluorescence imaging agents for molecular imaging. Herein we discuss advances in dendrimer-based contrast agents for molecular imaging focusing mainly on the chemical design as applied to optical, magnetic resonance, computer tomography, radionuclide, and multi-modality imaging.

[1]  Donald A Tomalia,et al.  Dendrimers in biomedical applications--reflections on the field. , 2005, Advanced drug delivery reviews.

[2]  C. Higgins,et al.  Influence of severity of myocardial injury on distribution of macromolecules: extravascular versus intravascular gadolinium-based magnetic resonance contrast agents. , 1997, Journal of the American College of Cardiology.

[3]  Marcelino Bernardo,et al.  A dendrimer‐based nanosized contrast agent dual‐labeled for magnetic resonance and optical fluorescence imaging to localize the sentinel lymph node in mice , 2007, Journal of magnetic resonance imaging : JMRI.

[4]  P. Choyke,et al.  Toward improved syntheses of dendrimer-based magnetic resonance imaging contrast agents: new bifunctional diethylenetriaminepentaacetic acid ligands and nonaqueous conjugation chemistry. , 2007, Journal of medicinal chemistry.

[5]  E. W. Meijer,et al.  Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[6]  R. Lauffer,et al.  Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. , 1999, Chemical reviews.

[7]  R. Birdwell Molecular Imaging: The Vision and Opportunity for Radiology in the Future , 2008 .

[8]  M. Brechbiel,et al.  Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice. , 2005, Kidney international.

[9]  Benjamin M Yeh,et al.  Dendritic iodinated contrast agents with PEG-cores for CT imaging: synthesis and preliminary characterization. , 2006, Bioconjugate chemistry.

[10]  C. Ozkan,et al.  Dendrimer-modified magnetic nanoparticles enhance efficiency of gene delivery system. , 2007, Cancer research.

[11]  J A Frank,et al.  Synthesis and relaxometry of high‐generation (G = 5, 7, 9, and 10) PAMAM dendrimer‐DOTA‐gadolinium chelates , 1999, Journal of magnetic resonance imaging : JMRI.

[12]  V. Pierre,et al.  Next generation, high relaxivity gadolinium MRI agents. , 2005, Bioconjugate chemistry.

[13]  D. Tomalia,et al.  Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging. , 2007, Biochemical Society transactions.

[14]  V. Jacques,et al.  Designing new MRI contrast agents: a coordination chemistry challenge , 1999 .

[15]  P. Choyke,et al.  Preparation and preliminary evaluation of a biotin-targeted, lectin-targeted dendrimer-based probe for dual-modality magnetic resonance and fluorescence imaging. , 2007, Bioconjugate chemistry.

[16]  Tristan Barrett,et al.  Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging. , 2007, ACS nano.

[17]  Hisataka Kobayashi,et al.  Micro-MRI methods to detect renal cysts in mice. , 2004, Kidney international.

[18]  Hisataka Kobayashi,et al.  Nano-sized MRI contrast agents with dendrimer cores. , 2005, Advanced drug delivery reviews.

[19]  D. Parker,et al.  In Vivo Evaluation of a PAMAM-Cystamine-(Gd-DO3A) Conjugate as a Biodegradable Macromolecular MRI Contrast Agent , 2007, Experimental biology and medicine.

[20]  Robert C. Brasch,et al.  Macromolecular contrast agents for MR mammography: current status , 2003, European Radiology.

[21]  A. Mohs,et al.  Polydisulfide Gd(III) chelates as biodegradable macromolecular magnetic resonance imaging contrast agents , 2006, International journal of nanomedicine.

[22]  Henrik S. Thomsen,et al.  Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents , 2007, Cancer imaging : the official publication of the International Cancer Imaging Society.

[23]  Hisataka Kobayashi,et al.  Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores. , 2003, Bioconjugate chemistry.

[24]  O. Nalcioglu,et al.  Regional comparison of tumor vascularity and permeability parameters measured by albumin‐GD‐DTPA and GD‐DTPA , 1995, Magnetic resonance in medicine.

[25]  R. Brasch,et al.  Rationale and applications for macromolecular Gd‐based contrast agents , 1991, Magnetic resonance in medicine.

[26]  Hisataka Kobayashi,et al.  Dendrimer-based nanosized MRI contrast agents. , 2004, Current pharmaceutical biotechnology.

[27]  R. Lauffer,et al.  Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design , 1987 .