title: Gd(III)-Dithiolane Gold Nanoparticles for T1-Weighted Magnetic Resonance Imaging of the Pancreas.
abstract: Pancreatic adenocarcinoma has a 5 year survival of approximately 3% and median survival of 6 months and is among the most dismal of prognoses in all of medicine. This poor prognosis is largely due to delayed diagnosis where patients remain asymptomatic until advanced disease is present. Therefore, techniques to allow early detection of pancreatic adenocarcinoma are desperately needed. Imaging of pancreatic tissue is notoriously difficult, and the development of new imaging techniques would impact our understanding of organ physiology and pathology with applications in disease diagnosis, staging, and longitudinal response to therapy in vivo. Magnetic resonance imaging (MRI) provides numerous advantages for these types of investigations; however, it is unable to delineate the pancreas due to low inherent contrast within this tissue type. To overcome this limitation, we have prepared a new Gd(III) contrast agent that accumulates in the pancreas and provides significant contrast enhancement by MR imaging. We describe the synthesis and characterization of a new dithiolane-Gd(III) complex and a straightforward and scalable approach for conjugation to a gold nanoparticle. We present data that show the nanoconjugates exhibit very high per particle values of r1 relaxivity at both low and high magnetic field strengths due to the high Gd(III) payload. We provide evidence of pancreatic tissue labeling that includes MR images, post-mortem biodistribution analysis, and pancreatic tissue evaluation of particle localization. Significant contrast enhancement was observed allowing clear identification of the pancreas with contrast-to-noise ratios exceeding 35:1.
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Radiology, and Center for Advanced Molecular Imaging, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Holbrook
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Radiology, and Center for Advanced Molecular Imaging, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Rammohan
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Radiology, and Center for Advanced Molecular Imaging, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Rotz
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Radiology, and Center for Advanced Molecular Imaging, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Keith W
authors.initials: KW
authors.lastname: MacRenaris
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Radiology, and Center for Advanced Molecular Imaging, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Preslar
authors.affiliation: Department of Chemistry, Molecular Biosciences, Neurobiology, Radiology, and Center for Advanced Molecular Imaging, Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meade
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry* / Q000493:pharmacokinetics; D006046:Gold / Q000737:chemistry*; D064593:Heterografts; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D058726:Nanoconjugates / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D010316:Particle Size; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D058726:Nanoconjugates; D013438:Sulfhydryl Compounds; D006046:Gold; D005682:Gadolinium
keywords: Pancreas; gold nanoparticles; magnetic resonance imaging