53675-30-2Relevant academic research and scientific papers
Development and biological evaluation of 99mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers
Akurathi, Vamsidhar,Dubois, Ludwig,Celen, Sofie,Lieuwes, Natasja G.,Chitneni, Satish K.,Cleynhens, Bernard J.,Innocenti, Alessio,Supuran, Claudiu T.,Verbruggen, Alfons M.,Lambin, Philippe,Bormans, Guy M.
, p. 374 - 384 (2014)
In vivo visualization of tumor hypoxia related markers, such as the endogenous transmembrane protein CA IX may lead to novel therapeutic and diagnostic applications in the management of solid tumors. In this study 4-(2-aminoethyl)benzene sulfonamide (AEBS, Ki = 33 nM for CA IX) has been conjugated with bis(aminoethanethiol) (BAT) and mercaptoacetyldiglycine (MAG2) tetradendate ligands and the conjugates radiolabelled with 99mTc, to obtain anionic and neutral 99mTc-labeled sulfonamide derivatives, respectively. The corresponding rhenium analogues were also prepared and showed good inhibitory activities against hCA IX (K i = 59-66 nM). In addition, a second generation bis AEBS was conjugated with MAG2 and labeled with 99mTc, and the obtained diastereomers were also evaluated in targeting CA IX. Biodistribution studies in mice bearing HT-29 colorectal xenografts revealed a maximum tumor uptake of 2 tetradendate ligands were more stable in plasma (>50% intact) compared to the neutral complex (28% intact). This preliminary data suggest that negatively charged 99mTc-labeled sulfonamide derivatives with modest lipophilicity and longer circulation time could be promising markers to target CA IX.
Reactivity of rhenium(V) oxo Schiff base complexes with phosphine ligands: Rearrangement and reduction reactions
Benny, Paul D.,Green, Jenny L.,Engelbrecht, Hendrik P.,Barnes, Charles L.,Jurisson, Silvia S.
, p. 2381 - 2390 (2005)
The symmetric rhenium(V) oxo Schiff base complexes frans-[ReO(OH 2)(acac2en)]Cl and trans-[ReOCl(acac2pn)], where acac2en and acac2pn are the tetradentate Schiff base ligands N,N'-ethylenebis(acetylacetone) diimine and N,N'- propylenebis(acetylacetone) diimine, respectively, were reacted with monodentate phosphine ligands to yield one of two unique cationic phosphine complexes depending on the ligand backbone length (en vs pn) and the identity of the phosphine ligand. Reduction of the Re(V) oxo core to Re(III) resulted on reaction of frans-[ReO-(OH2)(acac2en)]Cl with triphenylphosphine or diethylphenylphosphine to yield a single reduced, disubstituted product of the general type trans-[ReIII(PR 3)2(acac2en)]+. Rather unexpectedly, a similar reaction with the stronger reducing agent triethylphosphine yielded the intramolecularly rearranged, asymmetric cis-[ReVO(PEt 3)(acac2en)]+ complex. Reactions of frans-[RevO(acac2pn)CI] with the same phosphine ligands yielded only the rearranged asymmetric cis-[ReVO(PR3)(acac 2pn)]+ complexes in quantitative yield. The compounds were characterized using standard spectroscopic methods, elemental analyses, cyclic voltammetry, and single-crystal X-ray diffraction. The crystallographic data for the structures reported are as follows: frans-[ReIII(PPh 3)2(acac2en)]PF6 (H 48C48N2O2P3- Re·PF6), 1, triclinic (P1), a = 18.8261(12) A, b = 16.2517(10) A, c = 15.4556(10) A, α = 95.522(1)°, β = 97.130(1)°, γ = 91.350(1)°, V = 4667.4(5) A3, Z = 4; trans-[ReIII(PEt2Ph)2(acac 2en)]PF6 (H48C32N2O 2P2Re·PF6), 2, orthorhombic (Pccn), a = 10.4753(6) A, b = 18.4315(10) A, c = 18.9245(11) A, V = 3653.9(4) A3, Z = 4; cis-[ReVO(PEt 3)(acac2en)]PF6 (H33C 18N2O3PRe·1.25PF6), 3, monoclinic (C2/c), a = 39.8194(15) A, b = 13.6187(5) A, c = 20.1777(8) A, β = 107.7730(10)°, V = 10419.9(7) A3, Z = 16; cis-[ReVO(PPh3)(acac 2pn)]PF6 (H35C31N2O 3-PRe·PF6), 4, triclinic (P1), a = 10.3094(10) A, b = 12.1196(12) A, c = 14.8146(15) A, α = 105.939(2)°, β = 105.383(2)°, γ = 93.525(2)°, V = 1698.0(3) A3, Z = 2; cis-[ReVO(PEt 2Ph)(acac2pn)]PF6 (H35C 23N2O3PRe·PF6), 5, monoclinic (P21/n), a = 18.1183(18) A, b = 11.580(1) A, c = 28.519(3) A, β = 101.861(2)°, V = 5855.9(10) A3, Z = 4.
Coordination-Mediated Synthesis of Purification-Free Bivalent 99mTc-Labeled Probes for in Vivo Imaging of Saturable System
Taira, Yuichiro,Uehara, Tomoya,Tsuchiya, Masao,Takemori, Hideaki,Mizuno, Yuki,Takahashi, Shiori,Suzuki, Hiroyuki,Hanaoka, Hirofumi,Akizawa, Hiromichi,Arano, Yasushi
, p. 459 - 466 (2018/03/01)
In the synthesis of technetium-99m (99mTc) labeled target-specific ligands, the presence of a large excess of unlabeled ligands over 99mTc in the injectate hinders target accumulation of 99mTc-labeled ligands by competing for target molecules. To circumvent the problem, we recently developed a concept of the metal coordination-mediated multivalency, and proved the concept with a 99mTc-labeled trivalent compound [99mTc(CO)3(CN-RGD)3]+. In this study, D-penicillamine (Pen) was selected as a chelating molecule and a cyclic RGDfK peptide was conjugated to Pen via a hexanoic linkage (Pen-Ahx-c(RGDfK)). 99mTc complexation reaction, and the stability, integrin αvβ3 binding affinity, and biodistribution of the 99mTc-labeled probe were investigated to evaluate the applicability of the concept to bivalent probes. 99mTc-[Pen-Ahx-c(RGDfK)]2 was obtained over 95% radiochemical yields under low Pen-Ahx-c(RGDfK) concentration (50 μM). 99mTc-[Pen-Ahx-c(RGDfK)]2 showed approximately 10-times higher integrin αvβ3 binding affinity than the monovalent compounds, Pen-Ahx-c(RGDfK) and c(RGDyV). In biodistribution studies, the tumor accumulation of 99mTc-[Pen-Ahx-c(RGDfK)]2 was decreased to 77% and 43% of HPLC-purified (Pen-Ahx-c(RGDfK)-free) 99mTc-[Pen-Ahx-c(RGDfK)]2 by the presence of 5 nmol of unlabeled Pen-Ahx-c(RGDfK) and Re-[Pen-Ahx-c(RGDfK)]2, respectively. 99mTc-[Pen-Ahx-c(RGDfK)]2 provided tumor image without removing unlabeled ligand, while a 99mTc-labeled monovalent probe prepared from a monovalent ligand could not. These findings indicate the availability of the design concept to prepare 99mTc-labeled bivalent probes with a variety of 99mTc core and other metallic radionuclides of clinical relevance.
