[99mTcO] apcitide (99mTcO(P246)), the technetium complex of the 13 amino acid, apcitide, cyclo-(D-Tyr-Apc-Gly-Asp-Cys)-Gly-Gly-Cys(Acm)-Gly-Cys(Acm)-Gly-Gly-Cys-NH2, where Apc is L-[S-(3-aminopropyl)]cysteine (an arginine mimetic) and Acm is the acetamidomethyl protecting group, has high affinity and selectivity for the GPIIb/IIIa receptor that is expressed on the membrane surface of activated platelets and plays an integral role in platelet aggregation and thrombus formation. Bibapcitide, a 26 amino acid, bis-succinimidomethyl ether-linked dimer of the peptide apcitide has been formulated as a single-vial, lyophilized kit having the trade name AcuTect. When sterile, nonpyrogenic sodium pertechnetate (99mTcO4-) in 0.9% sodium chloride is added to the AcuTect radiopharmaceutical kit and the resulting kit is heated, [99mTcO] apcitide forms. This is the first radiopharmaceutical to target acute deep vein thrombosis (DVT) in the lower extremities. We report here the preparation, purification, and isolation of the 99Tc complex of apcitide and its characterization to determine the mode of binding of Tc to apcitide. [99TcO] apcitide was prepared, on the macroscopic level, by reaction of [99TcOCl4]- with apcitide, purified by preparative HPLC and isolated as a trifluoroacetate salt. [99TcO] apcitide can also be formed from the reaction of bibapcitide and 99TcO4- in the presence of Sn(II) and glucoheptonate at 80 degrees C, conditions that mimic the radiopharmaceutical kit preparation. FTIR data show a Tc=O stretch at 961.2 cm(-1), in the range observed for anionic [TcVO]3+ amide thiolate complexes. The mass spectral data is in agreement with the formula, [C51H73O20N17S5Tc]-, consistent with retention of Acm groups and the Tc binding in the Gly11-Gly12-Cys13 region of the peptide. Despite significant spectral overlap due to numerous similar amino acids, all protons of apcitide and [99TcO] apcitide were unambiguously assigned. The observation of two nonequivalent Acm groups and the observation of only 10 NH-CH cross-peaks in the TOCSY and COSY spectra of [99TcO] apcitide (NH-CH cross-peaks were absent for Gly11-Gly12-Cys13), compared to all 13 cross-peaks found in apcitide, provided compelling evidence to support the 99Tc binding to the terminal Gly11-Gly12-Cys13 region of apcitide.

We have isolated the 1:1 Ln:[alpha-2-P2W17O61]10- complexes for a series of lanthanides. The single-crystal X-ray structure of the Eu3+ analogue reveals two identical [Eu(H2O)3(alpha-2-P2W17O61)]7- moieties connected through two Eu-O-W bonds, one from each polyoxometalate unit. An inversion center relates the two polyoxometalate units. The Eu(III) ion is substituted for a [WO]4+ unit in the "cap" region of the tungsten-oxygen framework of the parent Wells-Dawson ion. The point group of the dimeric molecule is Ci. The extended structure is composed of the [Eu(H2O)3(alpha-2-P2W17O61)]214- anions linked together by surface-bound potassium cations. The space group is P, a = 12.7214(5) A, b = 14.7402(7) A, c = 22.6724(9) A, alpha = 71.550(3), beta = 84.019(3)degrees, gamma = 74.383(3), V = 3883.2(3) A3, Z = 1. The solution studies, including 183W NMR spectroscopy and luminescence lifetime measurements, show that the molecules dissociate in solution to form monomeric [Ln(H2O)4(alpha-2-P2W17O61)]7- species.

The alpha-1 and alpha-2 isomers of the monovacant Wells-Dawson heteropolyoxoanion [P(2)W(17)O(61)](10-) are complexants of trivalent rare-earth (RE) ions and serve to stabilize otherwise reactive tetravalent lanthanide (Ln) and actinide (An) ions in aqueous solution. Aspects of the bonding of Ln ions with alpha-1-[P(2)W(17)O(61)](10-) and alpha-2-[P(2)W(17)O(61)](10-) were investigated to address issues of complex formation and stability. We present structural insights about the Ln(III) coordination environment and hydration in two types of stoichiometric complexes, [Ln(alpha-1-P(2)W(17)O(61))](7-) and [Ln(alpha-2-X(2)W(17)O(61))(2)](17-) (for Ln identical with Sm, Eu, Lu; X identical with P, As). The crystal and molecular structures of [(H(2)O)(4)Lu(alpha-1-P(2)W(17)O(61))](7-) (1) and [Lu(alpha-2-P(2)W(17)O(61))(2)](17-) (2) were solved and refined through use of single-crystal X-ray diffraction. The crystallographic results are supported with corresponding insights from XAFS (X-ray absorption fine structure) for a series of nine solid-state complexes as well as from optical luminescence spectroscopy of the Eu(III) analogues in aqueous solution. All the Ln ions are eight-coordinate with oxygen atoms in a square antiprism arrangement. For the 1:1 stoichiometric Ln/alpha-1-[P(2)W(17)O(61)](10-) complexes, the Ln ions are bound to four O atoms of the lacunary polyoxometalate framework in addition to four O atoms from solvent (water) molecules as [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7-). This structure (1) is the first of its kind for any metal complex of alpha-1-[P(2)W(17)O(61)](10-), and the data indicate that the general stoichiometry [(H(2)O)(4)Ln(alpha-1-P(2)W(17)O(61))](7-) is maintained throughout the lanthanide series. For the 1:2 stoichiometric Ln/alpha-2-[X(2)W(17)O(61)](10-) complexes, no water molecules are in the Ln-O(8) coordination sphere. The Ln ions are bound to eight O atoms-four from each of two heteropolyanions-as [Ln(alpha-2-X(2)W(17)O(61))(2)](17-). The average Ln-O interatomic distances decrease across the lanthanide series, consistent with the decreasing Ln ionic radius.

AbstractIndazole‐based vitronectin receptor antagonists have been conjugated to chelators DOTA and Hynic using a variety of tethers and pharmacokinetic modifying groups. All modifications resulted in potent αvβ3 antagonists in an Elisa assay. The chelator conjugates were radiolabeled with 111In (DOTA) and 99mTc (Hynic) in >90% RCP. Biodistribution studies in the c‐Neu Oncomouse tumor model have shown high tumor uptake and primarily renal excretion for these agents. The potential use of these agents in cancer diagnosis will be discussed.

s: Abstracts of an International Conference on Peptide Radiopharmaceuticals in Diagnosis and Therapy Rome, Italy, 25-28 May 2000: Oral Presentations

The alpha-1 and alpha-2 [P2W17O61](10-) isomers, derivatives of the Wells-Dawson molecule, [alpha-P2W18O62](6-), may be useful ligands for stabilizing high-valent metal ions and lanthanides and actinides. However, the potential utility of the [alpha 1-P2W17O61](10-) ligand has not been realized. Specifically, for the lanthanides, the stoichiometry, structure, and purity of the lanthanide complexes of the [alpha 1-P2W17O61](10-) isomer are ambiguous. We have prepared lanthanide (Ln) complexes of the [alpha 1-P2W17O61](10-) isomer in greater than or equal to 98% isomeric purity, according to P-31 NMR data. W-183 NMR data clearly showed, for the first time, that the C-1 symmetry of the [alpha 1-P2W17O61](10-) lanthanide complexes was maintained in solution. We determined the stoichiometry of the lanthanide complexes of the [alpha 1-P2W17O61](10-) isomer in solution by two different methods: a complexometric titration method and excited state lifetime measurements and luminescence titrations for the europium(III) analogue. All experiments show a 1:1 Ln:[alpha 1-P2W17O61](10-) ratio. The P-31 NMR data showed that the lanthanides with smaller ionic radii (higher charge-size ratio) form stable complexes, even surviving crystallization from hot water. On the other hand, the lanthanum analogues were not stable in solutions of high lithium content. The tetrabutylammonium salt of the [Lu(alpha 1-P2W17O61)](7-) complex showed greater than or equal to 98% isomeric purity and the C-1 symmetry required for a derivative of [alpha 1-P2W17O61](10-). Also the tetrabutylammonium cation stabilized the [Lu(alpha 1-P2W17O61)](7-) complex; a mixed tetrabutylammonium, lithium salt was stable in water for weeks according to P-31 NMR spectroscopy.

Europium L3 edge X-ray absorption fine structure (XAFS) spectroelectrochemistry was used to determine the valence of europium in [Eu(α-2-As2W17O61)2]17− and [Eu(W5O18)2]9−. Dilute solutions of these anions in aqueous supporting electrolytes were examined at ambient temperature and at extreme potentials. In situ XANES (X-ray absorption near edge structure) data revealed that Eu is trivalent in both [Eu(α-2-As2W17O61)2]17− and [Eu(W5O18)2]9− at rest potential. Furthermore, it was not reduced to Eu2+ by constant-potential bulk electrolysis at significantly reducing potentials under the electrochemical conditions used herein. These results stand in obvious contrast to the redox behavior of [EuP5W30O110]12−, in which Eu3+ is reduced to Eu2+ under similar electrochemical conditions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Lanthanide complexes of three classes of polyoxoanions have been characterized by multinuclear (W-183 and P-31) NMR spectroscopy among other techniques. The tetrabutylammonium salt of the lacunary [alpha-2-P2W17O61](10-), prepared by metathesis of the potassium salt, was isomerically pure according to W-183 and P-31 NMR spectroscopy. The K-13[Ln(SiW11O39)(2)] family of complexes show a six-line pattern in the W-183 NMR spectrum at 40 degrees C for the lanthanum derivative, consistent with a symmetrical structure (C-2h or C-2r symmetry), and eleven-line patterns for the ytterbium and lutetium analogues at 23 degrees C, suggesting a lower symmetry (C-2) for complexes of the heavier lanthanide ions. The same phenomenon was observed for the [alpha-2-Ln(P2W17O61)(2)](17-) family of compounds. High-temperature W-183 NMR experiments on the [Lu(SiW11O39)(2)](13-) and the [alpha-2-Lu(P2W17O61)(2)](17-) compounds showed a reversible broadening and coalescence of the resonances, due to a dynamic effect, possibly rotation of the oxoanion ligands.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The preparation of the alpha-1 and alpha-2 isomers of the Wells-Dawson 17 tungsto derivatives by standard methods is accompanied by a significant proportion of the other isomer present as an impurity. In this study, the alpha-1 and alpha-2 isomers of [Zn(H2O)P2W17O61](8-) have been prepared in >98% purity by reacting isomerically pure K9Li-[alpha-1-P2W17O61] and K-10[alpha-2-P2W17O61], respectively, with ZnCl2, while rigorously controlling the pH at 4.7. The molecules were isolated as potassium salts. For W-183 NMR and P-31 NMR characterization, both molecules were ion exchanged by cation-exchange chromatography, maintaining the pH at 4.7, to obtain the lithium salts. Removal of water and isolation of a solid sample of [alpha-1-Zn(H2O)P2W17O61](8-) was achieved by lyophilization at -40 degrees C. The chemical shift data from P-31 and W-183 NMR spectroscopy of the isolated [alpha-1-Zn(H2O)P2W17O61](8-) and [alpha-2-Zn(H2O)P2W17O61](8-) isomers are consistent with a mixture of the alpha-1 and alpha-2 isomers reported previously;(1) the molecules have the expected C-1 and C-s symmetry, respectively. The [alpha-1-Zn(H2O)P2W17O61](8-) isomer is stable in the pH range of 4.6-6 at temperatures <35 degrees C. Using the same ion exchange and lyophilization techniques, the lacunary [alpha-1-P2W17O61](10-) isomer was isolated as the lithium salt; characterization by W-183 NMR spectroscopy confirms the C-1 symmetry.