title: Synthesis and metal complexation properties of Ph-DTPA and Ph-TTHA: novel radionuclide chelating agents for use in nuclear medicine.
abstract: We wish to report the synthesis and metal complexation properties of new radionuclide chelating agents for use in nuclear medicine. The strategy includes the facile preparation of rigid analogues of DTPA and TTHA possessing an aromatic ring. The aromatic structure used increased the stability of the complexes formed (pre-organization concept) and they are easily functionalised for attaching to any support. The poly(amino)poly(carboxylic) acids, Ph-DTPA (5a) and Ph-TTHA (5b) were obtained in five steps from phenylenediamine as the starting material with overall yields of 42 and 20%, respectively. The key step in this synthetic process is the preparation of tri- and tetra-amino compounds, 3a and 3b, respectively. In order to assess the ability of both ligands to complex with different metals ((111)In, (153)Sm, (90)Y, (177)Lu, (213)Bi, (225)Ac), along with their suitability for use in nuclear medicine, we used a number of complementary tests. We were able to demonstrate the high complexation capacity of Ph-DTPA (5a) with a broad range of radionuclides in a slightly acidic medium. In vitro stability studies show the high stability of Ph-DTPA with (111)In in human serum, a necessary condition for all medical applications. The protonation constant (log K(H)(i)) of Ph-DTPA (5a) was determined by potentiometric methods.
authors.affiliation: Laboratoire de Synthèse Organique, UMR CNRS 6513, Faculté des Sciences et des Techniques, 2, Rue de la Houssinière, BP 92208, 44072 Nantes Cedex, France.
authors.forename: Sebastien G
authors.initials: SG
authors.lastname: Gouin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gestin
authors.forename: Laurence
authors.initials: L
authors.lastname: Monrandeau
authors.forename: Fabienne
authors.initials: F
authors.lastname: Segat-Dioury
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Meslin
authors.forename: David
authors.initials: D
authors.lastname: Deniaud
mesh_terms: D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D004355:Drug Stability; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D019216:Metals, Heavy / Q000737:chemistry; D008674:Metals, Rare Earth / Q000737:chemistry*; D015394:Molecular Structure; D009683:Nuclear Medicine / Q000379:methods; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D016499:Radioimmunotherapy; D044967:Serum / Q000187:drug effects
chemical_list: D002614:Chelating Agents; D008024:Ligands; D019216:Metals, Heavy; D008674:Metals, Rare Earth; D009942:Organometallic Compounds; C511274:Ph-DTPA; C511275:Ph-TTHA; D004369:Pentetic Acid; C026059:triethylenetetraminehexaacetic acid; D004492:Edetic Acid