Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with 166Ho and 153Sm complexed to the bone seeking phosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD) and was complexed to lanthanide trivalent metal ions. This work is performed to utilise the idea that the energetic beta-particle emitter, 166 Ho, coupled with phosphonate ligands such as APD and APDDMP could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3+ and Sm3+ were measured by glass electrode potentiometry at 37 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from animal tests. The 166Ho-APDDMP complex was found to have little liver or bone uptake while 153Sm-APDDMP had a moderate bone uptake. This was primarily due to the high affinity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling.     

Chemical and biological evaluation of 153Sm and 166Ho complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid monoethylester) (H4 dotp OEt)

The novel methylphosphonic acid monoethylester (H₄dotp^OEt) has been synthesized and characterized and their complexes with Sm(III) and Ho(III) ions were studied. Dissociation constants of the ligand are lower than those of H₄dota. The stability constants of the Ln(III)-H₄dotp^OEt complexes are surprisingly much lower that those of H₄dota (H₄dota = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) probably due to a lower coordination ability of the phosphonate monoester groups. Acid-assisted decomplexation studies have shown that both complexes are less kinetically inert than the H₄dota complexes, but still much more inert than complexes of open-chain ligands. Nevertheless, the synthesis of ¹⁵³Sm and ¹⁶⁶Ho complexes with this ligand led to stable complexes both in vitro and in vivo. A very low binding of these complexes to hydroxyapatite (HA) and calcified tissues was observed confirming the assumption that a fully ionized phosphonate group(s) is necessary for a strong bone affinity. Both complexes show similar behaviour in vivo and, in general, follow the biodistribution trend of the H₄dota complexes with the same metals.     

(153)Sm(3+) and (111)In(3+) DTPA derivatives with high hepatic specificity: in vivo and in vitro studies

Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp (L(1)) and the ligand DTPA(BOM)(3) (BOM=benzyloxymethyl) (L(2)), radiolabelled with (153)Sm(3+) and (111)In(3+), were studied as potential hepatospecific gamma scintigraphic agents. In vivo studies with Wistar rats show that the main excretory pathway for all the chelates studied is the hepatobiliary system. The complexes of L(2) show even greater hepatobiliary specificity than L(1), perhaps as a consequence of longer blood circulation times due to their strong affinity towards HSA. The (153)Sm(3+) chelates are also more hepatospecific than the corresponding (111)In(3+) chelates. The La(3+) and In(3+) chelates of L(1) and L(2) show some structural and dynamic differences in aqueous solution, as studied by (1)H NMR spectroscopy. While only two nona-coordinated isomers were observed for the La(3+) complexes with both ligands, its number is much larger in the In(3+) complexes, with both octa- and hepta-coordinated species (with unbound side arms), as well as structural isomers for each coordination number.     

<Superscript>153</Superscript>Sm and <Superscript>166</Superscript>Ho complexes with tetraaza macrocycles containing pyridine and methylcarboxylate or methylphosphonate pendant arms

A set of tetraaza macrocycles containing pyridine and methylcarboxylate (ac₃py14) or methylphosphonate (MeP₂py14 and P₃py14) pendant arms were prepared and their stability constants with La³⁺, Sm³⁺, Gd³⁺ and Ho³⁺ determined by potentiometry at 25 °C and 0.10 M ionic strength in NMe₄NO₃. The metal:ligand ratio for ¹⁵³Sm and ¹⁶⁶Ho and for ac₃py14, MeP₂py14 and P₃py14, as well as the pH of the reaction mixtures, were optimized to achieve a chelation efficiency higher than 98%. These radiocomplexes are hydrophilic and have a significant plasmatic protein binding. In vitro stability was studied in physiological solutions and in human serum. All complexes are stable in saline and PBS, but 20% of radiochemical impurities were detected after 24 h of incubation in serum. Biodistribution studies in mice indicated a slow rate of clearance from blood and muscle, a high and rapid liver uptake and a very slow rate of total radioactivity excretion. Some bone uptake was observed for complexes with MeP₂py14 and P₃py14, which was enhanced with time and the number of methylphosphonate groups. This biological profile supports the in vitro instability found in serum and is consistent with the thermodynamic stability constants found for these complexes.     

Preparation and pharmacokinetics of samarium(III)-153-labeled DTPA-bis-biotin. Characterization and theoretical studies of the samarium(III)-152 conjugate.

The complex(153)Sm(III)DTPA-bis-biotin was prepared with a 99% radiochemical purity and a specific activity of 370 MBq/mg employing a molar ratio of DTPA-bis-biotin/Sm from 2 to 4 at pH 8.0. In vitro studies demonstrated that the complex is stable after dilution in saline and in human serum. Avidity of labeled biotin for avidin was not affected by the labeling procedure. Pharmacokinetic data of (153)Sm(III)DTPA-bis-biotin in normal mice showed that blood clearance is biexponential during the time interval from 0 to 24 h and that 3 h postinjection 92 +/- 4.32% of the dose is eliminated in the urine. To have further evidence which could sustain that (153)Sm(III)DTPA-bis-biotin is stable in solution as a real coordination complex, (152)Sm(III)DTPA-bis-biotin was obtained in macroscopic quantities and its characterization was done by IR, TGA, and conductivity measurements. The results indicated that the complex was chemically pure, where the Sm(3+) ion is neutralized by three carboxylate groups of the DTPA-bis-biotin ligand and coordinated to it. Using the Force Field method followed by ab initio calculations, the DTPA-bis-biotin and the Sm(III)DTPA-bis-biotin molecules were done. Accordingly, the coordination sphere of Sm(III) was totally satisfied with nitrogen and oxygen donors; the best coordination number was 9. The conformation geometry of both compounds is presented.     

Experience on the neutron activation of natural/enriched Re,Sm, and Ho nuclides in a reactor for the production of radiotherapeutic radionuclides

In recent years, much effort has been concentrated on the use of Β-emitting radionuclides for the treatment of various cancers. The reports suggested the application of¹⁸⁶Re and¹⁵³Sm as radiotherapeutic radionuclides for the treatment of palliative widespread skeletal métastases, whereas¹⁶⁶Ho was suggested as an agent for radiation synovectomy. Hence, a study on the production of¹⁸⁶Re,¹⁵³Sm, and¹⁶⁶Ho radionuclides was carried out by neutron activation of the appropriate target materials using a Pakistan Atomic Research Reactor (PARR-1) at a neutrons flux of 1 x 10⁴ n/cm² s. These radionuclides were then converted to appropriate radiopharmaceuticals for their use on animals and patients. The targets of natural Re (metal), natural Sm₂O₃, enriched Sm₂O₃ (99.06%), Sm(NO₃)₃ (solid), Sm(NO₃)₃ (liquid), and Ho₂O₃ were irradiated in the PARR-1. After irradiation, the purity of these radionuclides were checked by a multichannel analyzer, Canberra series 85 (MCA) coupled with HPGe detector and then measured in radioisotope calibrator Capintec ionization chamber model CRC-5RH. The effect of the irradiation time and amount of target material was investigated on the production yields of the radionuclides. The results showed an increase in the specific activity of Re with an increase in the irradiation time from 1 to 72 h, whereas a decrease in the specific activity was observed with increase in the amount of Re from 10 to 100 mg. Similar results were obtained for¹⁵³Sm and¹⁶⁶Ho radionuclides. The results further indicated that the specific activity of powder target was much less than the liquid targets for¹⁵³Sm. Their conversion to the appropriate radiotherapeutic radiopharmaceuticals were also carried out by investigating the experimental conditions and acceptable quality of¹⁸⁶Re-HEDP and¹⁵³Sm-EDTMP complexes were prepared. These complexes were then used on animals and patients which showed good performance.     

Antioxidation and DNA-Binding Properties of Binuclear Lanthanide(III) Complexes with a Schiff Base Ligand Derived from 8-Hydroxyquinoline-7-carboxaldehyde and Benzoylhydrazine

8-Hydroxyquinoline-7-carboxaldehyde (8-HQ-7-CA), Schiff-base ligand 8-hydroxyquinoline-7-carboxaldehyde benzoylhydrazone, and binuclear complexes [LnL(NO(3) )(H(2) O)(2) ](2) were prepared from the ligand and equivalent molar amounts of Ln(NO(3) )?6 H(2) O (Ln=La(3+) , Nd(3+) , Sm(3+) , Eu(3+) , Gd(3+) , Dy(3+) , Ho(3+) , Er(3+) , Yb(3+) , resp.). Ligand acts as dibasic tetradentates, binding to Ln(III) through the phenolate O-atom, N-atom of quinolinato unit, and C?N and ?O?C?N? groups of the benzoylhydrazine side chain. Dimerization of this monomeric unit occurs through the phenolate O-atoms leading to a central four-membered (LnO)(2) ring. Ligand and all of the Ln(III) complexes can strongly bind to CT-DNA through intercalation with the binding constants at 10(5) -10(6) M(-1) . Moreover, ligand and all of the Ln(III) complexes have strong abilities of scavenging effects for hydroxyl (HO(.) ) radicals. Both the antioxidation and DNA-binding properties of Ln(III) complexes are much better than that of ligand.     

Metal-ion speciation in blood plasma incorporating the bisphosphonate, 1-hydroxy-4-aminopropilydenediphosphonate (APD), in therapeutic radiopharmaceuticals.

In the quest for more effective pain palliation radiopharmaceuticals for metastatic bone cancer, this paper relates results obtained with 166Ho complexed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropililydenediphosphonate (APD). APD is itself a bone cancer pain palliation agent and this work was therefore driven by the idea that the energetic beta-particle emitter, 166Ho, coupled with APD could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants for important blood plasma metal-ions were measured by potentiometry or polarography at 37 degrees C and I = 150 mmol dm-3. The latter technique was used for systems where precipitates formed at ligand-to-metal ratios appropriate for potentiometry. For trivalent lanthanides, neither electrochemical technique could be used. Animal tests showed that the 166Ho-APD complex was taken up primarily by the liver due to precipitation or colloid formation.     

Radiolanthanide-labeled monoclonal antibody CC49 for radioimmunotherapy of cancer: biological comparison of DOTA conjugates and 149Pm, 166Ho, and 177Lu

The radiolanthanides 149Pm, 166Ho, and 177Lu have decay characteristics suitable for radioimmunotherapy (RIT) of cancer. N-Hydroxysulfosuccinimidyl DOTA (DOTA-OSSu) and methoxy-DOTA (MeO-DOTA) were conjugated to the anti-TAG-72 monoclonal antibody CC49 for radiolabeling with 149Pm, 166Ho, and 177Lu. While both DOTA conjugates could be labeled to high specific activity with 177Lu, MeO-DOTA afforded superior conjugate stability, radiolabeling, and radiochemical purity. Pilot biodistributions in nude mice bearing LS174T human colon carcinoma xenografts demonstrated that MeO-DOTA afforded higher tumor uptake and lower kidney retention of 177Lu than DOTA-OSSu. The in vitro stability of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 was evaluated using serum and hydroxyapatite assays. Serum stability of radiolanthanide-labeled MeO-DOTA-CC49 followed a trend based on the coordination energies of the radiometals, with 177Lu showing the highest stability after 96 to 168 h at 37 C. In contrast, MeO-DOTA-CC49 labeled with all three radiolanthanides was >92% stable to hydroxyapatite challenge for 168 h at 37 C. Comprehensive biodistributions of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 were obtained in LS174T-bearing nude mice. Maximum tumor uptakes were 100.0% ID/g for 149Pm at 96 h, 69.5% ID/g for 166Ho at 96 h, and 132.4% ID/g for 177Lu at 168 h. Normal organ uptakes were generally low, except in the liver, spleen, and kidney at early time points. By 96 to 168 h postinjection, nontarget organ uptake decreased to approximately 7% ID/g (kidney), 12% ID/g (spleen), and 20% ID/g (liver) for each radiolanthanide. When labeled with 149Pm, 166Ho, and 177Lu, MeO-DOTA-CC49 has potential for RIT of colorectal cancer and other carcinomas.     

Activated leukocyte cell adhesion molecule (ALCAM or CD166) modulates bone phenotype and hematopoiesis

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166), is expressed on osteoblasts (OB) and hematopoietic stem cells (HSC) residing in the hematopoietic niche, and may have important regulatory roles in bone formation. Because HSC numbers are reduced 77% in CD166^-/- mice, we hypothesized that changes in bone phenotype and consequently the endosteal niche may partially be responsible for this alteration. Therefore, we investigated bone phenotype and OB function in CD166^-/- mice. Although osteoclastic measures were not affected by loss of CD¹⁶⁶, CD166^-/- mice exhibited a modest increase in trabecular bone fraction (42%), and increases in osteoid deposition (72%), OB number (60%), and bone formation rate (152%). Cortical bone geometry was altered in CD166^-/- mice resulting in up to 81% and 49% increases in stiffness and ultimate force, respectively. CD166^-/- OB displayed elevated alkaline phosphatase (ALP) activity and mineralization, and increased mRNA expression of Fra 1, ALP, and osteocalcin. Overall, CD166^-/- mice displayed modestly elevated trabecular bone volume fraction with increased OB numbers and deposition of osteoid, and increased OB differentiation in vitro, possibly suggesting more mature OB are secreting more osteoid. This may explain the decline in HSC number in vivo because immature OB are mainly responsible for hematopoiesis enhancing activity.     

Lanthanide nitrate complexes of 4-N-(2′-Hydroxy-1 ′-naphthylidene)-aminoantipyrine

Lanthanide nitrates form with 4-N-(2′-hydroxy-l′- naphthylidene)aminoantipyrine (HNAAP) complexes of the type [Ln(HNAAP)₂(NO₃)₃] (where Ln = La, Pr, Nd, Sm, Gd, Tb, Dy, Ho and Y). The IR spectra of these complexes show that HNAAP acts as a bidentate neutral ligand and nitrate group is coordinated monodentately. The electronic spectra of the Nd complex show reasonable covalency in the metal-ligand bond. The magnetic moments of these complexes are in better agreement with the Van Vleck values. All these complexes are thermally stable up to200 °C.     

Heteroleptic phthalocyaninato-[2,3,9,10,16,17,23,24-octakis(octyloxy)phthalocyaninato] rare earth(III) triple-deckers: synthesis and spectroscopic characterization

The homo-dinuclear heteroleptic phthalocyaninato-[2,3,9,10,16,17,23,24-octakis(octyloxy)phthalocyaninato] rare earth(III) triple-decker complexes (Pc)M[Pc(OC₈H₁₇)₈]M[Pc(OC₈H₁₇)₈] (M=Pr, Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm) (1a–10a) and (Pc)M[Pc(OC₈H₁₇)₈]M(Pc) (M=Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm) (2b–10b) were obtained by condensation of bis(phthalocyaninato) rare earths M[Pc(OC₈H₁₇)₈]₂ (M=Pr, Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm), Li₂(Pc) and M(acac)₃·nH₂O (M=Pr, Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm). These novel compounds were characterized by ¹H NMR, mass, electronic absorption (UV–Vis), and IR spectroscopic methods.     

Internal heavy atom effect of Au(III) and Pt(IV) on hypocrellin A for enhanced in vitro photodynamic therapy of cancer

Hypocrellin A (HA), an a natural perylene quinine photosensitizers (PSs), can chelate with heavy metal ions, including Au(III) and Pt(IV), to form a 1:2 complex, which exhibits enhanced ¹O₂ generation quantum yield through the increased intersystem crossing efficiency mediated by internal heavy atom effect. Besides, the chelate process greatly improved the water solubility of HA. Comparative studies with HA and complexes have demonstrated that the heavy-atom effect on HA molecules enhances the efficiency of in vitro photodynamic (PDT) efficacy.     

An improved method for labeling monoclonal antibodies with samarium-153: use of the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6- methyldiethylenetriaminepentaacetic acid.

Samarium-153 (153Sm) radioimmunoconjugates of the monoclonal antibody K-1-21 were produced using the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6- methyldiethylenetriaminepentaacetic acid (Mx-DTPA). The specific activity (up to 150 MBq mg-1) and percent retained immunoreactivity (greater than 75%) were similar to that of 153Sm-K-1-21 conjugates formed with cyclic DTPA anhydride (cDTPAa). In vivo biodistribution studies showed specific localization of 153Sm-Mx-DTPA-K-1-21 to target antigen implants and higher blood pool and lower uptake in liver, spleen, kidney, and bone when compared to 153Sm-cDTPAa-K-1-21. The improved in vivo distribution of 153Sm-Mx-DTPA-K-1-21 should result in lower radiotoxicity to nontarget tissues when used for radioimmunotherapy purposes.     

153Sm radiotherapeutic bone agents

Samarium-153 is a radionuclide which can be produced in high yield by neutron irradiation and which has nuclear properties that make it attractive for use as a radiotherapeutic agent. Several phosphonate complexes of ¹⁵³Sm were synthesized and characterized by electrophoresis and HPLC. A procedure based on cation exchange chromatography was developed for measuring complex yields. The complexes could be produced in yields greater than 99%, were anionic, and most exhibited a single HPLC peak.     

Bisphosphonates as radionuclide carriers for imaging or systemic therapy

Bisphosphonates (BP's), biologically stable analogs of naturally occurring pyrophosphates, became the treatment of choice for pathologic conditions characterized by increased osteoclast-mediated bone resorption, namely Paget's disease, osteoporosis and tumor bone disease. Moreover, the clinical success of BP's is also associated with their use in (99m)Tc-based radiopharmaceuticals for bone imaging. In addition to the successful delivery of (99m)Tc (γ-emitter) to bone, BP's have also been used to deliver β(-)-particle emitting radiometals (e.g.(153)Sm, (186/188)Re) for bone-pain palliation. The main goal of this Review is to update the most recent research efforts toward the synthesis, characterization and biological evaluation of novel BP-containing radiometal complexes and radiohalogenated compounds for diagnostic or therapeutic purposes. The structure and in vivo properties of those compounds will be discussed and compared to the clinically available ones, namely in terms of image quality and therapeutic effect. We will also mention briefly the use of BP's as carriers of multimodal nuclear and optical imaging probes.     

Addition and reaction products of triethyl thiophosphate and metal perchlorates at just over ambient and elevated temperatures

Triethyl thiophosphate (tetp) invariably forms adducts with various metal perchlorates (M=Mg²⁺, Al³⁺, Cr³⁺, Mn²⁺, Fe²⁺, Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺) at 35–40°C in ethanol-triethyl orthoformate (teof). Only certain of these adducts, which involve S-bonded tetp in the thione form for soft or borderline metal ions and O-bonded tetp in the thiol tautomeric form for hard metal ions, could be isolated in solid form, owing to their tendency to decompose yielding diethylthiophosphato (detp) metal complexes and ethyl perchlorate, at temperatures ranging between ambient and 80–90°C, depending on the metal ion. Several well-defined detp and detpperchlorato metal complexes were obtained by heating solutions of mixtures of tetp and metal perchlorates in ethanol-teof at 80–90°C, and characterized. In most cases, linear polymeric or dimeric complexes involving double or triple bridges of O,S-bonded bidentate detp between adjacent metal ions were isolated. However, in a number of occasions, heavily hydrated monomeric species, containing terminal S-bonded detp were obtained.     

Interactions of tervalent lanthanide ions with bacterial collagenase (clostridiopeptidase A)

Tervalent cations of the lanthanide (rare-earth) elements reversibly inhibit bacterial collagenase (clostridiopeptidase A; EC 3.4.24.3). Sm(3+), whose ionic radius is closest to that of Ca(2+), is the most effective inhibitor, completely suppressing clostridiopeptidase activity at a concentration of 100mum in the presence of 5mm-Ca(2+). Er(3+) and Lu(3+), which both have ionic radii smaller than either Ca(2+) or Sm(3+), inhibit less efficiently, and La(3+), which is slightly larger than Ca(2+) or Sm(3+), inhibits only weakly. These findings indicate a closely fitting, stereospecific, Ca(2+)-binding pocket in clostridiopeptidase, which excludes ions that are only slightly larger than Ca(2+) [ionic radius 0.099nm (0.99 A)]. By contrast, trypsin, an enzyme whose activity does not depend on Ca(2+), requires lanthanide concentrations 50-100-fold greater for inhibition. Furthermore, the relative efficiency of inhibition of trypsin by lanthanides increases as the lanthanide ions become smaller and the charge/volume ratio increases. At a concentration of 50mum, Sm(3+) lowers the apparent K(m) for the hydrolysis of Pz-peptide by clostridiopeptidase from 5.4mm to 0.37mm and the apparent V(max.) from 0.29 Wünsch-Heidrich unit to 0.018 unit. Thus Sm(3+) enhances the affinity of this enzyme for its substrate; inhibition of hydrolysis of Pz-peptide may result from the excessive stability of the enzyme-Sm(3+)-substrate complex. Inhibition by Sm(3+) is competitive with regard to Ca(2+). The apparent dissociation constant, K(d), of Ca(2+) is 0.27mm, where the K(i) for Sm(3+) is 12mum. Clostridiopeptidase is more thermolabile in the absence of Ca(2+). With Sm(3+), thermoinactivation of the enzyme at 53 degrees C or 60 degrees C is initially accelerated, but then becomes retarded as heating continues. Lanthanide ions bind to gelatin and collagen. In so doing, they appear to protect these substrates from lysis by clostridiopeptidase through mechanisms additional to supplanting Ca(2+) at its binding site on the enzyme. Collagen and gelatin sequester sufficient lanthanide ions to gain partial protection from clostridiopeptidase in the absence of an extraneous source of these inhibitors.     

The [(99m)Tc(N)(PNP)](2+) metal fragment: a technetium-nitrido synthon for use with biologically active molecules. The N-(2-methoxyphenyl)piperazyl-cysteine analogues as examples

The incorporation of a bioactive molecule into a nitrido-containing (99m)Tc-complex has been successfully achieved by using the [TcN(PNP)](2+) metal fragment. In this strategy, the strong electrophilic [TcN(PNP)](2+) metal fragment efficiently reacts with bifunctional chelating ligands having a pi-donor atom set, such as N-functionalized O,S-cysteine. The 2-methoxyphenylpiperazine (2-MPP) pharmacophore, which displays preferential affinity for 5HT(1A) receptors, was conjugated to the amino group of cysteine to obtain 2-MPPP-cys-OS, where 2-MPPP is 3-[4-(2-methoxyphenyl)piperazin-1-yl]propionate. The asymmetric Tc(V)-nitrido complexes, [(99g/99m)Tc(N)(PNP)(2-MPPP-cys-OS)] (PNP = PNP3, PNP4), were obtained in high yield (95%), by simultaneous addition of PNP and 2-MPPP-cys-OS ligand to a solution containing a starting (99g)/(99m)Tc-nitrido precursor. A mixture of syn and anti isomers was observed, the latter being the thermodynamically favored species. In vitro challenge experiments using the anti isomers with glutathione and cysteine indicated that no transchelation reaction occurs. Assessment of the in vitro 5HT(1A) receptor-affinity of the technetium complexes revealed that only the anti-PNP4 complex possesses some affinity for the receptor, but displayed negligible brain uptake in biodistribution studies in rats in vivo.     

Crystal structures, DNA-binding studies and antioxidant activities of the Ln(III) complexes with 7-methoxychromone-3-carbaldehyde-isonicotinoyl hydrazone

The neutral mononuclear Ln(III) complexes (Ln = La, Sm) with 7-methoxychrom-one-3-carbaldehyde-isonicotinoyl hydrazone ligand (L) have been synthesized, characterized and investigated their interactions with calf-thymus DNA. The results show that the binding affinity of the La(III) complex is stronger than that of the Sm(III) complex and that of the ligand (L). Furthermore, the antioxidant activities of the ligand (L) and its Ln(III) complexes (Ln = La, Sm) were studied in detail.