title: Highly efficient technetium-99m labeling procedure based on the conjugation of N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine ligand with poly(ethylene glycol).
abstract: The PN(2)S N-(N-(3-diphenylphosphinopropionyl)glycyl)cysteine ligand was conjugated to methoxy-poly(ethylene glycol)-amino (mPEG-NH(2)) 5 and 20 kDa to yield PN(2)S(Trt)-PEG(5000) 1 and PN(2)S(Trt)-PEG(20000) 2, and then detritylated to PN(2)S-PEG(5000) 4 and PN(2)S-PEG(20000) 5. When an acidic solution of (99m)TcO(4)(-) is added to 4 or 5 in solid form, a quantitative yield in a single labeled species, (99m)Tc-labeled PN(2)S-PEG(5000) 9 and (99m)Tc-labeled PN(2)S-PEG(20000) 10, respectively, is obtained. The reaction occurs in less than 15 min at room temperature for 4 and 35 degrees C for 5. This labeling procedure avoids the use of an external reducing agent, and it is based on the amphiphilic properties of PN(2)S-PEGs. Once in water, 4 and 5 self-assemble in micelles, which catalyze the metal reduction by means of an electron pair transfer from the phosphorus to technetium. The [(99m)TcO](3+) species is then coordinated, and at micelle level, both the (P)ON(2)S and the PN(2)S coordinations are possible, as demonstrated by reacting (99m)Tc-gluconate and ReOCl(3)(PPh(3))(2) with 4 and 5 and with the oxidized analogous (P)ON(2)S-PEG(5000) 6. Compounds 9 and 10 exhibited a high stability both in vitro and in vivo. Biodistribution studies in mice also indicated that PN(2)S linking and (99m)Tc labeling do not modify PEG behavior in water and in vivo since the polymer dictates the fate of the conjugate.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, 35131 Padova, Italy. roberta.visentin@unipd.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Visentin
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pasut
authors.forename: Francesco Maria
authors.initials: FM
authors.lastname: Veronese
authors.forename: Ulderico
authors.initials: U
authors.lastname: Mazzi
mesh_terms: D000818:Animals; D003545:Cysteine / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods*; D013667:Technetium / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D008024:Ligands; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D011092:Polyethylene Glycols; D013667:Technetium; D003545:Cysteine