title: 99mTc-labeling of a hydrazinonicotinamide-conjugated vitronectin receptor antagonist useful for imaging tumors.
abstract: This report describes the (99m)Tc labeling of a HYNIC-conjugated vitronectin receptor antagonist (SQ168 = [2-[[[5-[carboonyl]-2-pyridinyl]hydrazono]methyl]benzenesulfonic acid]-Glu(cyclo[Lys-Arg-Gly-Asp-D-Phe])-cyclo[Lys-Arg-Gly-Asp-D-Phe]). The ternary ligand complex [(99m)Tc(SQ168)(tricine)(TPPTS)] (RP593) was prepared using a non-SnCl(2)-containing formulation. The corresponding (99)Tc analogue, [(99)Tc]RP593, was also prepared and characterized by HPLC and LC-MS. A HPLC concordance experiment using RP593 and [(99)Tc]RP593 showed that the same technetium complex was prepared at both the tracer and macroscopic levels. The LC-MS data is completely consistent with the 1:1:1:1 composition for Tc:SQ168:tricine:TPPTS and provides direct evidence that the two radiometric peaks in the radio-HPLC chromatogram of RP593 are indeed due to the resolution of diastereomers. In an in vitro receptor binding assay, [(99)Tc]RP593 was shown to have comparable binding affinity for the vitronectin receptor to that of SQ168 itself.
authors.affiliation: Medical Imaging Division, DuPont Pharmaceuticals Company,331 Treble Cove Road, North Billerica, Massachusetts 01862, USA. shuang.liu@dupontpharma.com
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: D S
authors.initials: DS
authors.lastname: Edwards
authors.forename: M C
authors.initials: MC
authors.lastname: Ziegler
authors.forename: A R
authors.initials: AR
authors.lastname: Harris
authors.forename: S J
authors.initials: SJ
authors.lastname: Hemingway
authors.forename: J A
authors.initials: JA
authors.lastname: Barrett
mesh_terms: D001667:Binding, Competitive / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004355:Drug Stability; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D013058:Mass Spectrometry; D009369:Neoplasms / Q000000981:diagnostic imaging; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011868:Radioisotopes / Q000737:chemistry*; D011877:Radionuclide Imaging; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D013667:Technetium / Q000737:chemistry*
chemical_list: D006834:Hydrazines; D015609:Organotechnetium Compounds; D010455:Peptides; D010456:Peptides, Cyclic; C436396:RP593; D011868:Radioisotopes; D019030:Receptors, Vitronectin; C117288:hydrazino nicotinamide; D009536:Niacinamide; D013667:Technetium