Chromatographic separation of selenium and arsenic: A potential (72)Se/(72)As generator.

An anion exchange method was developed to separate selenium and arsenic for potential utility in a (72)Se/(72)As generator. The separation of the daughter (72)As from the (72)Se parent is based on the relative acid-base behavior of the two oxo-anions in their highest oxidation states. At pH 1.5, selenate is retained on strongly basic anion exchange resin as HSeO4(-) and SeO4(2-), while neutral arsenic acid, H3AsO4, is eluted.

In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma.

Melanoma is a malignancy with increasing incidence. Although primary tumors that are localized to the skin can be successfully treated by surgical removal, there is no satisfactory treatment for metastatic melanoma, a condition that has currently an estimated 5-year survival of just 6%. During the last decade, ß- or α-emitter-radiolabeled peptides that bind to different receptors on a variety of tumors have been investigated as potential therapeutic agents in both the preclinical and clinical settings with encouraging results. A recent study demonstrated that 188-Rhenium ((188)Re)-labeled, via HYNIC ligand, fungal melanin-binding decapeptide 4B4 was effective against experimental MNT1 human melanoma and was safe to normal melanized tissues. The availability of radiolanthanides with diverse nuclear emission schemes and half-lives provides an opportunity to expand the repertoire of peptides for radionuclide therapy of melanoma. The melanin-binding decapeptide 4B4 was radiolabeled with (177)Lu, (166)Ho, and (153)Sm via a DO3A chelate. The stability studies of Ln*-DO3A-4B4 in phosphate-buffered saline, serum, and a hydroxyapatite assay demonstrated that (177)Lu-labeled peptide was more stable than (166)Ho- and (153)Sm-labeled peptides, most likely because of the smallest ionic radius of the former allowing for better complexation with DO3A. Binding of Ln*-DO3A-4B4 to the lysed highly melanized MNT1 melanoma cells demonstrated the specificity of peptides binding to melanin. In vivo biodistribution data for (177)Lu-DO3A-4B4 given by intraperitoneal administration to lightly pigmented human metastatic A2058 melanoma-bearing mice demonstrated very high uptake in the kidneys and low tumor uptake. Intravenous administration did not improve the tumor uptake. The plausible explanation of low tumor uptake of (177)Lu-DO3A-4B4 could be its decreased ability to bind to melanin during in vitro binding studies in comparison with (188)Re-HYNIC-4B4, exacerbated by the very fast clearance from the blood and the kidneys "sink" effect.

Tetradentate bis-phosphine ligands (P(2)N(2) and P(2)S(2)) and their Rh(III), Ni(II) and (105)Rh complexes: X-ray crystal structures of trans-[RhCl(2)(L2)]PF(6), [Ni(L2)](PF(6))(2) and µ-O(2)SO(2)-[Ni(L5)](2)(PF(6))(2).

INTRODUCTION: Tetradentate acyclic and macrocyclic diphosphine ligands (P(2)N(2) and P(2)S(2)) have been synthesized and characterized as potential chelates for Rh(III). METHODS: The coordination complexes [RhCl(2)(L1)]Cl, trans-[RhCl(2)(L2)]PF(6), [Ni(L2)](PF(6))(2), [Ni(L3)](PF(6))(2), [RhCl(2)(L4)]PF(6) and [RhCl(2)(L5)]PF(6) have been synthesized and characterized. In addition, radiochemistry studies of the (105)Rh complexes with the ligands N,N'-bis[2-(diphenylphosphino)phenyl]-1,3-diaminopropane (L1), 4,8-diphenyl-1,11-diaza-4,8-diphosphaundecane (L2), 5,9-diphenyl-5,9-diphospha-2,12-dithiatridecane (L3) and 1,4,8,11-tetraphenyl-4,8-diphospha-1,11-dithiaundecane (L4) are reported, including normal mouse biodistributions of (105)Rh-L2. RESULTS: trans-[RhCl(2)(L2)]PF(6) crystallized in the monoclinic space group P2(1)/c with a = 9.9353(5) Å, b = 9.0929(5) Å, c = 28.689(1) Å, ß = 93.1400(10) deg, Z = 4, R = 0.037 and R(w) = 0.053. [Ni(L2)](PF(6))(2) crystallized in the monoclinic space group P2(1)/c with a = 11.9665(6) Å, b = 14.8903(7) Å, c = 31.148(1) Å, ß = 91.587(1) deg, Z = 8, R = 0.056 and R(w) = 0.083. µ-O(2)SO(2)-[Ni(L5)](2)(PF(6))(2), an unusual sulfate-bridged Ni(II) dimer, crystallized in the triclinic space group P1 bar with a = 15.179(2) Å, b = 15.514(2) Å, c = 16.128(2) Å, α = 105.280(7) deg, ß = 113.074(6) deg, γ = 101.657(8) deg, Z = 2, R = 0.050 and R(w) = 0.072. CONCLUSIONS: Phosphine-containing ligands allowed for lower temperatures and lower ethanol concentrations in the formulations for (105)Rh(L) complexation, but at the expense of higher ligand concentrations.

Gold(III) bis-thiosemicarbazonato complexes: synthesis, characterization, radiochemistry and X-ray crystal structure analysis.

INTRODUCTION: A variety of (bis)thiosemicarbazone-based ligand systems have been investigated as chelating agents for Au(III) complexes with potential radiotherapeutic applications. Ligand systems containing an ethyl, propyl or butyl backbone between the two imine N donors have been synthesized to evaluate chelate ring size effects on the resultant Au(III) complex stability at the macroscopic and radiotracer levels. METHODS: The Au(III) complexes were synthesized and characterized by NMR, electrospray ionization mass spectra, elemental analysis and X-ray crystallography. The (198)Au complexes were evaluated in vitro at the tracer level for stability in phosphate-buffered saline at pH 7.4 and 37 degrees C. One of these complexes [(198)Au(3,4-HxTSE)] showed high in vitro stability and was further evaluated in vivo in normal mice. RESULTS: [Au(ATSM)]AuCl(4).2CH(3)OH, (ATSM=diacetyl-bis(N(4)-methylthiosemicarbazone)) H(14)C(8)N(6)O(2)S(2)Cl(4)Au(2).2CH(3)OH, crystallized from methanol in the monoclinic space group P21/n with a=14.7293(13) A, b=7.7432(7) A, c=20.4363(18) A, beta=100.140(2) degrees, V=2294.4 (4) A(3), Z=4; [Au(3,4-HxTSE)]Cl.CH(3)CH(2)OH/AuCl(2), (3,4-HxTSE=3,4-hexanedione-bis(N(4)-ethylthiosemicarbazone)) H(26)C(13.6)N(6)O(0.8)S(2)Cl(1.2)Au(1.2), crystallized from ethanol in the monoclinic space group P21/c with a=10.1990(10) A, b=13.8833(14) A, c=15.1752(15) A, beta=99.353(2) degrees , V=2120.2 (4) A(3), Z=4. CONCLUSIONS: These studies revealed poor stability of the [(198)Au][Au(3,4-HxTSE)](+) complex; however, crystal structure data suggest potential alterations to the ligand backbone may increase stability.