LuCl3 Research Articles

Emerging Radionuclides in a Regulatory Framework for Medicinal Products - How Do They Fit?

Recent years have seen the establishment of several radionuclides as medicinal products in particular in the setting of theranostics and PET. [177Lu]Lutetium Chloride or [64Cu]Copper Chloride have received marketing authorization as radionuclide precursor, [68Ga]Gallium Chloride has received regulatory approval in the form of different 68Ge/68Ga generators. This is a formal requirement by the EU directive 2001/83, even though for some of these radionuclide precursors no licensed kit is available that can be combined to obtain a final radiopharmaceuticals, as it is the case for Technetium-99m. In view of several highly promising, especially metallic radionuclides for theranostic applications in a wider sense, the strict regulatory environment poses the risk of slowing down development, in particular for radionuclide producers that want to provide innovative radionuclides for clinical research purposes, which is the basis for their further establishment. In this paper we address the regulatory framework for novel radionuclides within the EU, the current challenges in particular related to clinical translation and potential options to support translational development within Europe and worldwide.

Novel synthesis, characterization and optical properties of Lu2O3 deposited by electrochemical method

Lutetium oxide Lu2O3 thin films were synthesized for the first time onto Fluorine doped Tin Oxide (FTO) and stainless steel substrates using the conventional electrochemical deposition method from lutetium chloride precursor. The as-prepared films were characterized by X-ray diffraction (XRD), Rietveld method, Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS) and the optical properties UV–vis. The formation mechanisms from aqueous medium were determined. The as-deposited oxide was found to be single pure bixbyite type structure with space group Ia3¯. UV–vis spectroscopy showed that the Lu2O3 film had an optical band gap of 5.1eV.

Structure of the solvation spheres of ions in aqueous solutions of LuCl3 according to X-ray diffraction data

A model approach based on the experimental XRD data was used for aqueous solutions of lutetium chloride in a wide range of concentrations under the standard conditions. The parameters of the nearest environment of ions were determined. The coordination number of the lutetium ion in solutions without solvent deficiency was found to be eight. The cation was also found to form the second coordination sphere. The transition to the concentrated and saturated solutions led to a decrease in the number of water molecules in the first sphere of the cation to six. Noncontact ion associates were shown to be characteristic for all systems under study.

Sandwich complexes of lutetium with tetraanthraquinoneporphyrazine and asymmetric alkoxy-substituted phthalocyanines. Preparation and spectral properties

Interaction of 3,6-di(hexadecyloxy)phthalonitrile with tetrachlorophthalonitrile and lutetium chloride in alcoholic medium yields lutetium complexes with asymmetric phthalocyanines. Their heating with dinitrile of anthraquinone-2,3-dicarboxylic acid gives the sandwich complexes containing fragments of tetraanthraquinoneporphyrazine and asymmetric phthalocyanines; their spectral properties has been studied.

An X-ray diffraction study of aqueous solutions of lutetium trichloride

The X-ray diffraction analysis is used to study aqueous solutions of lutetium chloride in a wide concentration range under standard conditions. Small angle peaks on the functions of the X-ray scattering intensity and the maxima of radial distribution functions of the atomic-electron density are interpreted. It is found that highly concentrated solutions are characterized by a unique quasi-crystalline structure distinguished by short- and long-range ordering. Dilution of solutions results in that the own structure of the solvent starts to play the major role in the structure of the systems. It is established for the first time that small angle peaks on the scattering intensity functions are also manifested for diluted solutions, which indicates that long-range ordering is preserved in them.

Reactivity of Rare-Earth Metal Complexes Stabilized by an Anilido-Phosphinimine Ligand

Treatment of anilido-phosphinimine-ligated yttrium mono(alkyl) complex 1a, LY(CH2Si(CH3)(3))(THF) (L = o-(2,6-(C6H3Pr2)-Pr-i)NC6H4P(C6H4)(C6H5)N(2,4,6-C6H2Me3)), with 2 equiv of phenylsilane in DME afforded methoxy-bridged complex 2, [LY(mu-OCH3)](2), via the corresponding hydrido intermediate. When excess isoprene was added to the mixture of la and phenylsilane, a eta(3)-isopentene product, 3, LY(CH2C(CH3)=CHCH3)(THF), was isolated. A lutetium chloride, LLuCl(DME) (4), was generated through the reaction of lutetium mono(alkyl) complex 1b, LLu(CH2Si(CH3)(3))(THF), with [Ph3C]-[B(C6F5)(4)]center dot LiCl accompanied by the formation of [Li(DME)(3)](+)[B(C6F5)(4)](-). Metathesis reaction of 1b with excess AlMe3 at room temperature gave a methyl-terminated counterpart, 5, LLu(CH3)(THF)(2). In all these reactions, the Ln-C-phenyl bonds of complexes 1 remained untouched.

(2,5‐Bis{[(2,6‐diisopropylphenyl)imino]methyl}pyrrolyl)yttrium and ‐lutetium Complexes – Synthesis and Structures

AbstractThe reaction of 2,5‐bis{[(2,6‐diisopropylphenyl)imino]methyl}pyrrole (dip2‐pyr)H with nBuLi and KH resulted in the lithium compound [(dip2‐pyr)Li] and the potassium compound [(dip2‐pyr)K], respectively. Transmetallation of [(dip2‐pyr)Li] with YCl3 in thf afforded the “ate complex” [(dip2‐pyr)YCl3Li(thf)3], in which an additional equivalent of LiCl is coordinated as a four‐membered Li–Cl–Y–Cl metallacycle. In contrast, treatment of [(dip2‐pyr)K] with anhydrous yttrium and lutetium trichloride resulted in [(dip2‐pyr)LnCl2(thf)2] (Ln = Y, Lu). Obviously, by using the potassium reagent [(dip2‐pyr)K] the formation of “ate complexes” is inhibited. Reaction of NaC5H5 with [(dip2‐pyr)YCl3Li(thf)3] or [(dip2‐pyr)YCl2(thf)2] afforded the metallocene [(dip2‐pyr)Y(η5‐C5H5)2]. A significant difference in reactivity between the compounds [(dip2‐pyr)YCl3Li(thf)3] and [(dip2‐pyr)YCl2(thf)2] could not be observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Synthesis and properties of lanthanide complexes with tetrapyrazinoporphyrazine and its substituted derivatives

Reactions of dicyanopyrazine and its tert-butyl-, diphenyl-, and dipyridyl-substituted derivatives with erbium, thulium, ytterbium, and lutetium chlorides, acetates, and acetylacetonates gave the corresponding tetrapyrazinoporphyrazine metal complexes which were characterized by elemental analyses, and IR, 1H NMR, and electronic absorption spectra. The stability of the complexes to thermooxidative decomposition in air was also studied.

Syntheses and structures of mononuclear lutetium imido complexes with very short Lu–N bonds

The reaction of 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-imine (ImDippNH) with trimethylsilylmethyllithium and anhydrous lutetium trichloride affords the imido complex [LuCl2(ImNDipp)(THF)3], which, on further reaction with dipotassium cyclooctatetraenide, K2(C8H8), leads to the half-sandwich cyclooctatetraenyl complex [(eta8-C8H8)Lu(ImNDipp)(THF)2]; both complexes contain very short Lu-N bond lengths, which are shorter than any previously reported Lu-N distances.

Cation size dependent reactivity of lanthanide trihalides with bulky alkylcyclopentadienyl anions

Reactions of NdCl3 and PrCl3 with two equivalents of sodium tri-tert-butylcyclopentadienide furnished base- and salt-free [Cp′2NdCl] and [Cp′2PrCl] (Cp′ = 1,2,4-(Me3C)3C5H2) in good yield. Trimethylaluminium has been added to the neodymium complex to form [Cp′2NdClAlMe3]. With LaCl3 or CeCl3 base-free bis(ring) complexes were not obtained, but in the latter case the salt adduct [(4Cp2Ce)(μ-Cl)2Na(tmeda)2]∞ (4Cp = (Me2CH)4C5H) could be extracted from the product mixture with tetramethylethylenediamine and crystallized as a zigzag chain polymer. [4Cp2SmCl2Na(dme)2] retained the coordinated sodium chloride even when dissolved in non-polar solvents. Attempted preparation of [Cp′2YbCl] gave the mono(ring) complex [Cp′YbCl(μ-OCH2CH2OCH3)]2 from cleavage of the dimethoxyethane solvent and with lutetium trichloride the hexanuclear complex [(4CpLu)5LuCl13(OEt2)5] was prepared in low yield. For lanthanum and thulium use of the triiodide as a starting compound enabled synthesis of the corresponding bis(tetraisopropylcyclopentadienyl)metal iodide, bis{tri-tert-butylcyclopentadienyl}lanthanum iodide was also prepared from LnI3. [4Cp2TmI] shows a unique conformation of one of the tetraisopropylcyclopentadienyl ligands with two isopropyl neighbours rotated towards each other indicating extreme steric congestion. Oxidation of [Cp′2Sm] with copper(I) iodide gave [Cp′2SmI] in high yield. Mono(ring) complexes are readily available from trichlorides of thulium, ytterbium, and lutetium. Apart from the donor solvent adducts [4CpTmCl2(dme)], [Cp′YbCl2(thf)2], and [4CpLuCl2(dme)], which were isolated from solutions in the corresponding donor solvent, the salt- and donor-free dihalides [Cp′TmCl2]n and [Cp′YbCl2]n were obtained as oligomers from pentane or petroleum ether extracts. The thulium compound gave [Cp′Tm{N(SiMe3)2}2] with two equivalents of Na[N(SiMe3)2] and the ytterbium complex underwent ring exchange with lithium tert-butylcyclopentadienide and formation of the bis(tert-butylcyclopentadienyl)ytterbium complex [(Me3CC5H4)2Yb(μ-Cl)]2.

A Chiral-Bridged Aminotroponiminate Complex of Lutetium as Catalyst for the Asymmetric Hydroamination

The enantiomerically pure bridged aminotroponiminate S,S-H2{(iPrATI)2diph}, in which two amino-isopropyl-troponimine moieties are linked by 1,2-(S,S)-diamino-1,2-diphenylethane, has been prepared. The chiral lutetium alkyl complex of composition [(R,R)-{(iPrATI)2diphLuCH2SiMe3(THF)] (3) was obtained via two synthetic approaches. In the first approach the dipotassium salt [(S,S)-K2{(iPrATI)2diph}] (1) of the ligand was reacted via a salt metathesis with lutetium trichloride to give [(S,S)-{(iPrATI)2diph}LuCl(THF)] (2). Reaction of 2 with LiCH2SiMe3 resulted in 3. Compound 3 can also be obtained by the reaction of [Lu(CH2SiMe3)3(THF)2] with (S,S)-H2{(iPrATI)2diph} under elimination of Me4Si. The alkyl complex 3 was used as catalyst in the intramolecular hydroamination reaction of nonactivated terminal aminoolefins. Good catalytic activities and moderate enantioselectivties were observed.

In vitro and in vivo evaluation of 177Lu- and 90Y-labeled E. coli heat-stable enterotoxin for specific targeting of uroguanylin receptors on human colon cancers

The human E. coli heat-stable enterotoxin (ST(h), amino acid sequence N1SSNYCCELCCNPACTGCY19) binds specifically to the guanylate cyclase C (GC-C) receptor, which is present in high density on the apical surface of normal intestinal epithelial cells as well as on the surface of human colon cancer cells. Analogs of ST(h) are currently being used as vectors targeting human colon cancers. Previous studies in our laboratory have focused on development of 111Indium-labeled ST(h) analogs for in vivo imaging applications. Here, we extend the scope of this work to include targeting of the therapeutic radionuclides 90Y and 177Lu. The peptide DOTA-F19-ST(h)(1-19) was synthesized using conventional Fmoc-based solid-phase techniques and refolded in dilute aqueous solution. The peptide was purified by RP-HPLC and characterized by MALDI-TOF MS and in vitro receptor binding assay. The DOTA-conjugate was metallated with nonradioactive Lu(III)Cl3 and Y(III)Cl3, and IC50 values of 2.6+/-0.1 and 4.2+/-0.9 nM were determined for the Lu- and Y-labeled peptides, respectively. 177Lu(III)Cl3 and 90Y(III)Cl3 labeling yielded tracer preparations that were inseparable by C18 RP-HPLC, indicating that putative differences between Lu-, Y- and In coordination spheres are not observed in the context of labeled ST(h) peptides. In vivo biodistribution studies of the 177Lu-labeled peptide in severe combined immunodeficient (SCID) mice bearing T-84 human cancer tumor xenografts showed rapid clearance from the bloodstream, with >90 %ID in the urine at 1 h pi. Localization of the tracer within tumor xenografts was 1.86+/-0.91 %ID/g at 1 h pi, a value higher than for all other tissues with the exception of kidney (2.74+/-0.24 %ID/g). At 24 h pi, >98 %ID was excreted into the urine, and 0.35+/-0.23 %ID/g remained in tumor, again higher than in all other tissues except kidney (0.91+/-0.46 %ID/g). Biodistribution results at 24 h pi for the 90Y-labeled peptide mirrored those for the 177Lu analog, in agreement with the identical behavior of the labeled analogs by C18 RP-HPLC. These results demonstrate the ability of 177Lu- and 90Y-labeled ST(h) molecules to specifically target GC-C receptors expressed on T-84 human colon cancer cells.

Preparation of Nanocrystalline Lu2O3:Eu Phosphor via a Molten Salts Route.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The First Example of μ-η2:η2-Peroxo-Bridged Macrocyclic Lanthanide Complex. The Crystal Structure of [Lu2{Me2pyo[16]trieneN5}2(μ-η2:η2-O2)Cl2](ClO4)2Dioxane Solvate

The crystal structure of [Lu2{Me2pyo[16]trieneN5}2(μ-η 2:η 2-O2)Cl2](ClO4)2(1), where Me2pyo[16]trieneN5 is 2,14-dimethyl-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19),2,13,15,17-pentaene reveals the biologically significant – unprecedented among the lanthanide macrocyclic complexes – planar side-on μ-η 2:η 2 coordination mode of the peroxide as a result of [1 + 1] template Schiff base cyclocondensation of 2,6-diacetylpyridine with 3,7-diazanonane-1,9-diamine in the presence of mixed lutetium chloride and perchlorate salts followed by slow crystallization process.

Preparation of nanocrystalline Lu2O3:Eu phosphor via a molten salts route

The paper reports on the course of decomposition of hydrated lutetium nitrate and lutetium chloride to Lu2O3 in the eutectic mixture of NaNO2 and KNO2. It was shown that a crystallographically pure phase of the cubic Lu2O3 is formed at temperature as low as 250°C. IR spectra revealed that the recovered powder contains some OH-contamination, however. The powders are characterized by crystallites sizes in the range of 18–30nm in average. Emission and excitation spectra of Eu-doped powders show characteristic features for Eu3+ ion in an oxide host, which indicates that the procedure is appropriate for making activated nanoparticulate oxide phosphors. Most profound emission appears around 611nm and the luminescence from the powder made starting with Lu(NO3)3 was noticeably higher compared to the product obtained from LuCl3. The excitation spectrum of Eu3+ emission at 611nm contains a band related to the fundamental absorption of the lutetia host lattice, which indicates an existence of the host-to-activator energy transfer.

Sterically Demanding Chelating Diamide Complexes of Yttrium and Lutetium

Deprotonation of the bridged diamine ArHN(CH2)3NHAr (Ar = 2,6-iPr2C6H3) with n-butyllithium and potassium hydride, respectively, gives the corresponding alkali metal derivatives M2{ArN(CH2)3NAr} (M = Li (1a), K (1b)). 1a reacts with yttrium trichloride to form the metalate complex [Y{ArN(CH2)3NAr}(THF)2(μ-Cl)2Li(THF)2] (2). The coordination number of yttrium in 2 is six. The structure of 2 shows two bridging chloride ligands and an alkali metal bound by two solvate molecules. Further reaction of 2 with NaC5H5 in THF affords the complex [Y{ArN(CH2)3NAr}(η5-C5H5)(THF)] (4). The structure of 4 in solution and in the solid state is best described as a distorted tetrahedron. Reaction of 1b with anhydrous lutetium trichloride leads to the unexpected ionic product [LuCl2(THF)5][Lu{ArN(CH2)3NAr}2] (5). 5 can be formally considered as a derivative of the ionic compound [LuCl2(THF)5][LuCl4(THF)2], in which all four chlorine atoms of the anion are substituted by 2 equiv of the {ArN(CH2)3NAr}2- ligand. As seen from all three structures, the steric demand of the {ArN(CH2)3NAr}2- ligand is less than that of two (C5Me5)- moieties.

Cyclooctatetraene complexes of yttrium and the lanthanides with chiral and achiral aminotroponiminates

The combination of dilithium-1,4-bis(trimethylsilyl)cyclooctatetraene, Li 2{1,4-(Me 3Si) 2C 8H 6}, with anhydrous yttrium or lutetium trichloride and potassium N-isopropyl-2-(isopropylamino)troponiminate, K{( i Pr) 2ATI}, leads to the corresponding mono cyclooctatetraene complexes [{η 8-1,4-(Me 3Si) 2C 8H 6}Ln{( i Pr) 2ATI}(THF)] (Ln=Y ( 1a), Lu ( 1b)). The solid-state structure of 1a was established by single-crystal X-ray diffraction. Using the same synthetic strategy, the chiral complex [{η 8-1,4-(Me 3Si) 2C 8H 6}Y{(( S)-PhCHCH 3) 2ATI}(THF)] ( 2) can be obtained by using the enantiomerically pure ligand, potassium N-( S)-1-phenylethyl-2-(( S)-1-phenylethylamino)troponiminate, K{(( S)-PhCHCH 3) 2ATI}. Furthermore, [(η 8-C 8H 8)Sm{( i Pr) 2ATI}(THF)] ( 3) was obtained by the reaction of [(C 8H 8)SmI(THF)] and K{( i Pr) 2ATI}.

Structure model and synthesis of NdCl 3 -FeCl 3 -graphite intercalation compounds

The distribution of the elements and microstructure of NdCl 3 -FeCl 3 -graphite intercalation compounds (GICs) were shown by scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). The results show that Nd element intercalates into graphite, forming NdCl 3 -FeCl 3 -GICs, and the distribution of Nd and Fe is nearly even. On the basis of the data, a structure model for RECl 3 -GICs was founded, and the characteristic layer distance and the index of interval energy were calculated. The calculated results agree with experimental ones, and the relative errors are ±2%. Thus it can be seen that the (111) face is optimal direction for intercalation reaction of TbCl 3 —LuCl 3 , and the (001) face is that for LaCl 3 —GdCl 3 , because of the lowest interval energy.

Bridged aminotroponiminate complexes of lutetium

The reaction of the salt di-potassium-1,3-di(2-(isopropylamino)troponiminate)-propane, K 2[( i Pr)TP], with lutetium trichloride leads to [[( i Pr)TP]LuCl] 2 ( 1). 1 was characterized by single crystal X-ray crystallography. To study the reactivity of 1 some selected derivatives such as alkyl, amide, η 5-cyclopentadienyl, and η 3-borohydride complexes were synthesized by substitution of the chlorine atom of 1.

Molecular structure of lutetium trichloride monomer and dimer

This paper reports on a simultaneous electron diffraction and mass spectrometric study of the saturated vapor of lutetium trichloride at T = 1070(10) K. It is found that the vapor consists of the monomer LuCl3 [91.6(1.2) mol. %] and dimer Lu2Cl6. The following parameters were obtained for LuCl3 (rg configuration): rg(Lu-Cl) = 2.403(5) A, rg(CL.Cl) = 4.119(18) A,g(Cl-Lu-Cl) = 117.9(1.3)ℴ. Calculation of vibrational corrections for a transition from rg to rα geometry gave a planar equilibrium configuration for LuCl3 with D3h symmetry, whereas our previous electron diffraction study recommended a pyramidal configuration. Possible reasons for this controversy are discussed. The geometry of the Lu2Cl6 molecule of D2h symmetry is described by the following parameters (ra configuration): rα(Lu-Clt) = 2.366(5) A, rα(Lu-Clα) = 2.589(24) A, ZClt-rLu-Clt = 119(7)ℴ, ZClb-Lu-Clb = 84(2)ℴ. The mean energies of the terminal [E(Lu-Clt) = 485 kJ/mole] and bridging [E(Lu-Clb) = 292 kJ/mole] bonds of Lu2Cl26 are estimated.