Albumin microaggregates for radioactive scanning of reticuloendothelial systems
AssigneeNew England Nuclear Corporation
InventorEugene L. Saklad
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Abstract
Microaggregates of a complex of (1) albumin, particularly human serum albumin and (2) a metal reducing agent, particularly a stannous reducing agent, preferably formed in the presence of a stabilizing ligand, which complex, when labelled with technetium-99m provides an excellent agent for imaging reticuloendothelial systems (RES), particularly the liver, spleen, and bone marrow; methods of making and using the same; a complex (physical or chemical) of technetium-99m with such microaggregates and methods of using such latter complex.
Claims65
A composition for labelling with Tc-99m for radioactive imaging comprising microaggregates of albumin and a reducing metal.
A composition for labelling with Tc-99m for radioactive imaging comprising microaggregates of albumin and a reducing metal, said composition also comprising an additional stabilizing ligand for said reducing metal selected from the group consisting of a phosphonate, a phosphate, an aminocarboxylate, a polyhydroxycarboxylate and a polycarboxylate.
A composition for labelling with Tc-99m for radioactive imaging comprising microaggregates of albumin and a reducing metal, at least 90% of said microaggregates being not greater than 5 .mu.m in particle size, and at least 40% of said microaggregates being between 0.2 and 5 .mu.m in particle size.
A radioactive imaging agent comprising Tc-99m labelled microaggregates of albumin and a reducing metal, wherein at least 90% of said microaggregates have a particle size not greater than 5 .mu.m and at least 40% of said microaggregates are between 0.2 and 5 .mu.m.
A radioactive imaging agent comprising Tc-99m labelled microaggregates of human serum albumin and a stannous reducing metal, said agent also comprising a stabilizing ligand for said reducing metal selected from the group consisting of phosphonates, phosphates, aminocarboxylates, polyhydroxycarboxylates and polycarboxylates.
A radioactive imaging agent comprising Tc-99m labelled microaggregates of albumin and a reducing metal, said agent also comprising a diphosphonate stabilizing ligand for said reducing metal.
A radioactive imaging agent comprising Tc-99m labelled microaggregates of human serum albumin and a stannous reducing metal, at least 90% of said microaggregates having a particle size no greater than 5 .mu.m and not substantially more than 50% of said microaggregates being less than 0.2 .mu.m, said agent stabilized with non-aggregated human serum albumin and buffer, said microaggregates being microaggregated at a pH of 4.5-9.5 but on the alkaline side of the apparent isoelectric point of said albumin.
A method for making an agent for labelling with Tc-99m for radioactive imaging, said method comprising microaggregating albumin in the presence of a reducing metal.
A method for making an agent for labelling with Tc-99m for radioactive imaging, said method comprising microaggregating human serum albumin in the presence of a stannous reducing metal, said microaggregation being carried out in the presence of a stabilizing ligand for said reducing metal selected from the group consisting of a phosphonate, a phosphate, an aminocarboxylate, a polyhydroxycarboxylate and a polycarboxylate.
A method of imaging the RES of a primate comprising injecting into the primate Tc-99m-labelled microaggregates of HSA and a reducing metal to concentrate said Tc-99m-labelled microaggregates in the RES.
A method for imaging the RES of a primate comprising injecting into the primate a composition comprising Tc-99m-labelled microaggregates of HSA and a stannous reducing metal to concentrate said Tc-99m-labelled microaggregates in the RES, said composition containing a diphosphonate stabilizing ligand for said reducing metal.
A preaggregated bulk, containing human serum albumin to be aggregated to microaggregates for radioactive labelling for use as an RES imaging agent, comprising a solution of unaggregated and undenatured human serum albumin, reducing metal and stabilizing ligand for said reducing metal, said bulk having a pH of between 4.5 and 9.5 but on the alkaline side of the isoelectric point of said albumin, the amount of ligand being sufficient to stabilize said stannous ions and prevent precipitation thereof before microaggregation but insufficient to provide any substantial non-RES target seeking properties when the microaggregates subsequently formed from said bulk are radioactively labelled and utilized for RES imaging.
A preaggregated bulk containing human serum albumin to be aggregated to microaggregates for radioactive labelling for use as an RES imaging agent, comprising a solution of unaggregated and undenatured human serum albumin, stannous reducing metal and stabilizing ligand for said reducing metal, said bulk having a pH of between 5.6 and 6.5 but on the alkaline side of the isoelectric point of said albumin, the amount of ligand being sufficient to stabilize said stannous ions and prevent precipitation thereof before microaggregation but insufficient to provide any substantial non-RES target seeking properties when the microaggregates subsequently formed from said bulk are radioactively labelled and utilized for RES imaging, said ligand being a diphosphonate selected from the group consisting of methylene diphosphonate and hydroxyethylene diphosphonate.
A method for making an agent for labelling with Tc-99m for radioactive imaging, said method comprising microaggregating albumin in the presence of a reducing metal, at a pH between 3.5 and 9.5 but at a pH away from the apparent isoelectric point of said albumin.
Dependencies are inferred from the claim text.