Abstract: A method of sterilizing a nanoparticle preparation at a high temperature is provided. A plurality of nanoparticles are purified to form the preparation, wherein the nanoparticles comprise at least a core and a shell and the shell comprises one or more ligand species attached to the core. The nanoparticle preparation is made by a purified nanoparticle composition, a carrier fluid and an excess of the one or more ligand species not attached to the core. The ligand species attached to the core and the excess ligand species added after purification are structurally identical. The nanoparticle preparation provided by the present invention may be used as contrast agents in medical imaging techniques such as X-ray and magnetic resonance imaging.

Abstract: A contrast agent composition and a method of diagnostic imaging are provided. The composition comprises a pharmaceutically acceptable carrier and a metal-complex comprising a ligand having structure (XXX): wherein R1, R2, R3, R7, R8, R?1, R?2, R?3, R7? and R8? are selected form hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group; R4, R?4 are selected from a hydrogen, a hydroxyl, a protected hydroxyl group, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; n is an integer between 0 and 4; R5, R?5 are selected from a hydrogen, a protecting group comprising C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals, m is an integer between 1 and 10; at least one of R7 and R?7 is acidic groups or protected acidic groups; Y comprises a protein or peptide moiety, a particle, a micelle, a liposome, an organic molecule, oligomer, polymer or a hydrophilic moiety.

Abstract: Disclosed are novel cold fixation methods and reagents comprising contacting a biological sample with a reagent for fixation at a temperature of less than 20° C. where the reagent comprises an aqueous buffer, a water soluble alkylnitrile, C2 to C6 alkyl ester, or combination thereof, and formaldehyde to the aqueous buffer solution and removing the biological sample from contact with the reagent.

Abstract: The invention provides a coverslip for automated decoverslipping of a tissue bearing slide comprising a horizontal base portion having a length, width, and height, at least two side wall portions extending downward from opposite sides of the base portion each having a length and width and h; and wherein the total wall volume to base volume ratio is greater than or equal to approximately 0.025.

Abstract: A method of diagnostic imaging is disclosed comprising administering a medical formulation to a subject, the formulation comprising a contrast enhancement agent having structure I and salts thereof wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is one or more charge balancing counterions; and one or more pharmaceutically acceptable carriers and excipients. The subject is subjected to a diagnostic imaging technique such as magnetic resonance imaging. The technique may be used in a variety of diagnostic imaging regimes, such as imaging of circulatory systems, genitourinary systems, hepatobiliary systems, central nervous systems, tumors, and abscesses among others.

Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I and salts thereof wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is one or more charge balancing counterions. Also provided are a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement agent I.

Abstract: A chelating agent, a metal-chelate, and a contrast agent are provided, wherein the chelating agent comprises a compound of structure (I) wherein R1, R2, R3, R8, R7, R?7 R?1, R?2, R?3 and R8? are selected from a hydrogen, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; R4 and R?4 are selected from a hydrogen, a hydroxyl group, a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; n is an integer between 0 and 4; R5 and R?5 are selected from a hydrogen, a protecting group selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals; R9 and R?9 are selected form a hydrogen or a protecting group selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals, m is an integer between 0 and 10; and at least one of R7 and R?7 is acidic group or a protected acidic group.

Abstract: A contrast agent composition and a method of diagnostic imaging are provided. The composition comprises a pharmaceutically acceptable carrier and a metal-complex comprising a ligand having structure (XXX): wherein R1, R2, R3, R7, R8, R?1, R?2, R?3, R7? and R8? are selected form hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group; R4, R?4 are selected from a hydrogen, a hydroxyl, a protected hydroxyl group, a protected C1-C3 hydroxyalkyl group, a C1-C3 alkyl group; n is an integer between 0 and 4; R5, R?5 are selected from a hydrogen, a protecting group comprising C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, C2-C30 aromatic radicals, m is an integer between 1 and 10; at least one of R7 and R?7 is acidic groups or protected acidic groups; Y comprises a protein or peptide moiety, a particle, a micelle, a liposome, an organic molecule, oligomer, polymer or a hydrophilic moiety.

Abstract: A method of sterilizing a nanoparticle preparation at a high temperature is provided. A plurality of nanoparticles are purified to form the preparation, wherein the nanoparticles comprise at least a core and a shell and the shell comprises one or more ligand species attached to the core. The nanoparticle preparation is made by a purified nanoparticle composition, a carrier fluid and an excess of the one or more ligand species not attached to the core. The ligand species attached to the core and the excess ligand species added after purification are structurally identical. The nanoparticle preparation provided by the present invention may be used as contrast agents in medical imaging techniques such as X-ray and magnetic resonance imaging.

Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I wherein R1 is independently at each occurrence a hydroxy group, a C1-C3hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3hydroxyalkyl group; and wherein Q is a charge balancing counterion. Also provided is a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement I.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XX wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence a protecting group is selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, and C2-C30 aromatic radicals.

Abstract: Provided herein are chelator-functionalized nanoparticles comprising a passive core; and an active coating that demonstrate T1 magnetic resonance pattern upon exposure to a magnetic field. Also provided are methods of making such chelator-functionalized nanoparticles as well as imaging methods using the nanoparticles.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XX wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence a protecting group is selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, and C2-C30 aromatic radicals.

Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I and salts thereof wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is one or more charge balancing counterions. Also provided are a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement agent I.

Abstract: A method of diagnostic imaging is disclosed comprising administering a medical formulation to a subject, the formulation comprising a contrast enhancement agent having structure I and salts thereof wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is one or more charge balancing counterions; and one or more pharmaceutically acceptable carriers and excipients. The subject is subjected to a diagnostic imaging technique such as magnetic resonance imaging. The technique may be used in a variety of diagnostic imaging regimes, such as imaging of circulatory systems, genitourinary systems, hepatobiliary systems, central nervous systems, tumors, and abscesses among others.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XX wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence a protecting group is selected from the group consisting of C1-C30 aliphatic radicals, C3-C30 cycloaliphatic radicals, and C2-C30 aromatic radicals.

Abstract: In one aspect, the present invention provides a contrast enhancement agent comprising an iron chelate having structure I wherein R1 is independently at each occurrence a hydroxy group, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R2-R7 are independently at each occurrence hydrogen, a C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R1-R7 is a hydroxy group or a C1-C3 hydroxyalkyl group; and wherein Q is a charge balancing counterion. Also provided is a metal chelating ligand having structure IX and medical formulations comprising the contrast enhancement I.

Abstract: In one aspect, the present invention provides a protected ligand precursor having structure XXI wherein R8 is independently at each occurrence a protected hydroxy group, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, and b is 0-4; R9-R11 are independently at each occurrence hydrogen, a protected C1-C3 hydroxyalkyl group, or a C1-C3 alkyl group, with the proviso that at least one of R8-R11 is a protected hydroxy group or a protected C1-C3 hydroxyalkyl group; and R12 and R13 are independently at each occurrence acid sensitive protecting groups.

Abstract: A method of conjugating a carboxylate-containing molecule to an amine-containing macromolecule to form a substituted macromolecule is provided. The method includes (a) forming a first solution by dissolving a substance comprising at least one macromolecule having free amine groups in an aqueous basic solution; (b) forming a second solution by combining at least one carboxylate-containing molecule with at least one acid acceptor in an aprotic solvent; (c) adding at least one carboxylate activating agent to the second solution to form an activated carboxylate-containing molecule; (d) combining the first solution and second solutions to form a multiphasic solution; and (e) isolating the resultant substituted macromolecule from the mixture. A substituted macromolecule produced by the aforementioned method is also provided.

Abstract: Provided herein are chelator-functionalized nanoparticles comprising a passive core; and an active coating that demonstrate T1 magnetic resonance pattern upon exposure to a magnetic field. Also provided are methods of making such chelator-functionalized nanoparticles as well as imaging methods using the nanoparticles.