Evaluation of 99mTc-HIDA complex as a cholescintigraphic agent (author's transl)

In the reaction labeling N-(2,6-dimethylphenylcarbamoylmethyl) iminodiacetic acid (HIDA) with 99mTc, several complexes with different chemical characteristics were observed to occur with slight changes in the labeling conditions. Among these complexes, a complex detected in the bile of rats was limited to one complex, named as complex II. The preparation method of 99mTc-HIDA complex II and the exchange reaction between this complex and penicillamine indicate that 99mTc is coordinated with HIDA as low-hydrolyzed 99mTc in this complex. This complex is excreted rapidly through the bile and within 1 hr, about 65% of the total activity injected is recovered from bile in rats. The organ distribution of this complex was studied in mice by radioassay and in rabbits by scintillation camera and, in both cases, the radioactivity was accumulated in the gallbladder. These results suggest that the 99mTc chemical state, low-hydrolyzed state, relates to the bile excretion behavior of this complex, a potentially useful cholescintigraphic agent.     

Inflammation-induced synergetic enhancement of nanoparticle treatments with DOXIL<Superscript>®</Superscript> and <Superscript>90</Superscript>Y-Lactosome for orthotopic mammary tumor

Polymeric micelles (Lactosome) in the size of 20–30 nm were labeled with radionuclides of ¹¹¹In (¹¹¹In-DOTA-Lactosome) for SPECT imaging and ⁹⁰Y (⁹⁰Y-DOTA-Lactosome) for β-ray irradiation for mammary tumor in mice. The tumor site at the femoral right leg grafted with 4T1 cells was clearly imaged at 24 h after the intravenous injection. Biodistribution revealed that the half-life time of ¹¹¹In-DOTA-Lactosome was 11 h, which enabled the nanoparticle selectively accumulated in tumor site due to the enhanced permeability and retention (EPR) effect. The anti-tumor therapeutic effect of ⁹⁰Y-DOTA-Lactosome was observed depending on the dose frequency and amount. Under the condition of the percutaneous ethanol injection treatment, the therapeutic effect of ⁹⁰Y-DOTA-Lactosome was enhanced due to the super EPR effect. Owing to the super EPR effect, co-administration of ⁹⁰Y-DOTA-Lactosome and DOXIL^® inhibited the tumor growth during 15 days with their administrations.     

Photo‐ and pH‐Responsive Polycarbonate Block Copolymer Prodrug Nanomicelles for Controlled Release of Doxorubicin

Photo/pH dual‐responsive amphiphilic diblock copolymers with alkyne functionalized pendant o‐nitrobenzyl ester group are synthesized using poly(ethylene glycol) as a macroinitiator. The pendant alkynes are functionalized as aldehyde groups by the azide‐alkyne Huisgen cycloaddition. The anticancer drug doxorubicin (DOX) molecules are then covalently conjugated through acid‐sensitive Schiff‐base linkage. The resultant prodrug copolymers self‐assemble into nanomicelles in aqueous solution. The prodrug nanomicelles have a well‐defined morphology with an average size of 20–40 nm. The dual‐stimuli are applied individually or simultaneously to study the release behavior of DOX. Under UV light irradiation, nanomicelles are disassembled due to the ONB ester photocleavage. The light‐controlled DOX release behavior is demonstrated using fluorescence spectroscopy. Due to the pH‐sensitive imine linkage the DOX molecules are released rapidly from the nanomicelles at the acidic pH of 5.0, whereas only minimal amount of DOX molecules is released at the pH of 7.4. The DOX release rate is tunable by applying the dual‐stimuli simultaneously. In vitro studies against colon cancer cells demonstrate that the nanomicelles show the efficient cellular uptake and the intracellular DOX release, indicating that the newly designed copolymers with dual‐stimuli‐response have significant potential applications as a smart nanomedicine against cancer.     

Core-excited states of Fe from the Fe(p, t)Fe reaction at 52 MeV

The perturbation theory for projected states is applied to the two-level pairing force model. Both approximate and exact forms of number projection are considered. The results are compared with the exact ones and with ordinary perturbation theory based on BCS wave functions without projection.     

99mTc-2-mercaptopropionylglycine: different biliary excretion behavior in different animal species (author's transl)

Labeling of 2-mercaptopropionylglycine (2-MPG) with 99mTc, was studied and its chemical characteristics were examined. Further, biliary excretion behavior of this complex was comparatively estimated in mice, rats, and rabbits. 99mTc-2-MPG was rapidly excreted in large quantities into the bile in mice and rats: within 1 hr after injection, 51% of the injected dose was recovered from the bile in rats. On the other hand, the ligand exchange reaction between this complex and penicillamine indicates that a low hydrolyzed 99mTc species is coordinated with 2-MPG. These results suggest that a low hydrolyzed 99mTc is an effective feature in biliary excretion behavior of 99mTc compounds. Another interesting in vivo behavior of 99mTc-2-MPG is the difference observed in mice and rabbits: in mice, very high 99mTc activity is concentrated in the gallbladder and the clearance from tissues other than the gallbladder is rapid, whereas in rabbits, although a rapid and high excretion into the gallbladder is observed, a considerable high 99mTc activity is retained in the liver and the kidney. One reasons for this different in vivo behavior is the low stability of this complex at high dilution: a big animal has the large dilution volume which lead to higher decomposition estimated by the higher liver and kidney retention or the lower bile excretion. In conclusion, studies carried on 99mTc-2-MPG showed a good biliary excretion behavior but an in vivo unstableness in big animals.     

Polarographic studies on bipyridine complexes: III. Polarography of tris(2,2′-bipyridine) complexes of chromium(I), chromium(0), vanadium(0), titanium(0) and molybdenum(0)

Polarograms and cyclic voltammograms for tris(2,2′-bipyridine) complexes of V(0), Cr(0), Cr(I), Ti(0) and Mo(0) in N,N-dimethylformamide are reported. The reversible half-wave potentials for the following redox systems in lower oxidation states are determined: Cr(?I)/Cr(?II), Cr(?II)/Cr(?III), V(I)/V(0), V(0)/V(?I), V(?I)/V(?II), V(?II)/V(?III), Ti(0)/Ti(?I), Ti(?I)/Ti(?II), Mo(?I)/Mo(?II) and Mo(?II)/Mo-(?III). On the basis of the half-wave-potential shift caused by the methyl substitution of ligands, it is concluded that each excess electron of the reductant species of the redox systems, V(bipy)₃^?/V(bipy)₃^2?, Cr(bipy)₃/Cr(bipy)₃^?, Cr(bipy)₃^?/Cr(bipy)₃^2? and Cr(bipy)₃^2?/Cr(bipy)₃^3? (bipy=2,2′-bipyridine), occupies a ligand π^*-orbital and that of the V(bipy)₃²⁺/V(bipy)₃⁺ and V(bipy)₃⁺/V(bipy)₃ systems a metal t_2g-orbital. The apparent π-character of the excess electron of the redox systems Cr(bipy)₃⁺/Cr(bipy)₃ and V(bipy)₃/V(bipy)₃^? is discussed. It is pointed out that the relative electron affinities of trisbipyridine complexes can be determined from the half-wave potential data. The lowest π^*-orbitals of V(bipy)₃^?, Cr(bipy)₃ and Fe(bidy)₃²⁺ become higher in this order. This suggests that the electrostatic interaction between a π^*-electron and the residual charge on the central metal ion predominantly accounts for the observed π^*-level shift.     

The effect of the central metal charge on the reduction half-wave potentials of d6 metal complexes

A SCF MO calculation is made to obtain the energies of the lowest vacant π-orbitals of tris-2,2′-bipyridine complexes of d⁶ transition metals in various oxidation states. Any overlap of a metal t_2g-orbital and a ligand π-orbital is neglected and the metal ion is considered as a source of an electrostatic potential field. The π-electron system of the three ligand molecules is treated as a whole by taking account of the overlap of 2pπ-AO's belonging to different ligand molecules. When it is assumed that a ligand π^*-orbital is occupied by the electron added in the course of reduction, the results of the calculation and the Born equation for solvation energy together lead to a linear relation between the reduction half-wave potentials of the complexes and the sum of the charges on the central metal ion and the ligand nitrogen atoms. This linear relation is confirmed experimentally by using the available data on the reduction half-wave potentials of the tris-bipyridine complexes of the following d⁶ metals: Ir(III), Fe(II), Ru(II), Os(II), Cr(0), Mo(0), V(?I) and Ti(?II).