Complex metal-DTPA

Medical applications are so far limited in number, but gadolinium complexes of DTPA and other hgands have become highly important injectible MRI contrast agents (see Metal-based Imaging Agents). The luminescent properties of the lanthanides are becoming exploited in luminescent sensors and bioassays. 

This results in higher efficiency compared to the usual sequestering agents such as EDTA, NTA, and DTPA. Another advantageous difference to this kind of sequestering agent is the diminished aggressiveness towards metals and metal ions. Ions of Cu and Cr in metallized Reactive and Direct dyestuffs are not attacked by BURCO NBS LIQUID, dye shade and fastness of reactive dyes or direct dyestuffs which contain complexed metal ions, and are therefore not impaired. 

Ion-pair chromatography is also suited for the analysis of metal complexes. For their chromatographic separation, the complexes must be thermodynamically and kinetically stable. This means that complex formation must be thermodynamically possible and furthermore an irreversible process. Metal-ETDA and metal-DTPA complexes exhibit a corresponding high stability. To separate the Gd-DTPA complex (Fig. 5-21), which is of great relevance in the pharmaceutical industry, TBAOH was used as the ion-pair reagent [36], Detection was carried out by measuring the electrical conductivity in combination with a suppressor system. 

The concentration of (EDTA) ", and thus the ability to complex metal ions, will depend upon the pH. A decrease in pH results in an increase in the deprotonation of EDTA and hence an increase in the concentration of the ED I A ion. The effect of this is that only metal ions with a very high affinity for EDTA will be able to form stable complexes. The stability constants for the EDTA and [diethylenetriaminepentaacetic acid] - (DTPA ) complexes with some important metal ions that are of particular interest for chelation therapy are listed in Table 7.3. It is important to note that the stability of the EDTA and DTPA complexes with toxic metals, such as lead, mercury, cadmium, or plutonium are quite similar to those with essential metals such as zinc, cobalt or copper however, the Ca complex is many orders of magnitude lower. This has important implications for chelation therapy. First, the mobilization and excretion of zinc and other essential metals are likely to be increased, along with that of the toxic metal during EDTA treatment and secondly, the chelation of the ionic calcium in the blood, that can cause tetany and even death, can be avoided by administering the chelator as the calcium salt. 

In the case of metal incorporation, the Carbon/Metal molar ratio was chosen in order to theoretically obtain 1% weight metal samples (without carbon loss during drying and pyrolysis). The complexant/metal molar ratio (DTPA/M) was kept at 1 for palladium-DTPA samples. 

Comparisons to the known structure of indium DTPA and to other divalent metal DTPA bis-amide complexes indicate that the indium cation binds to the three amine nitrogen atoms, the four carboxylate oxygen atoms, and the one carboxairdde oxygen atom of the DTPA monoamide ligand. Addition of an acidic In chloride solution to a ly-ophilized DTPA-octreotide pellet at room temperature readily fomis In DTPA-octreotide, known clinically as OctreoScan. In a rat model of pancreatic carcinoma In DTPA-octreotide showed clear visualization of the tumors and rapid, primarily renal, clearance of the radiophamiaceutical/ Moreover, pretreatment with 1 mg of octreotide prevents uptake of " in DTPA-octreotide in the tumors and adrenal glands, an observation that verifies that this radiolabeled peptide binds to receptor sites. 

Alkyl pyrocatechol extractants provide greater group separation factors. Eu/Am separation factors of 70 have been reported for a non-equilibrium extraction in the system 4-(a,(z-dioctylethyl)-pyrocatechol/NaOH/DTPA (diethylenetriamine-N, N, N, N, N-pentaacetic acid) (or DTPP - diethylenetriamine-N, N, N, N", N"-pentameth-ylenephosphonic acid) (Karalova et al. 1982). The separation factors are based mainly on the difference in the rates of the metal-DTPA (or DTPP) complexation equilibria for Eu and Am. They are therefore highly dependent on the contact time. A principal limitation of the practical application of such a separation scheme is the relatively long contact times (> 10 min) required for extraction. However, the slow equilibration compares favorably with that for other lanthanide-actinide separation processes (e.g. TALSPEAK, section 7). 

Crystal structures of Ln complexes of DTPA and DOTA derivatives show that Ln +-bound diethylenetriamine moieties in these complexes always occur either in the 88 or in the X.X. conformation (Scheme 5.10). In these complexes, the steric interactions are always minimized. Upon coordinated by a metal ion, the central nitrogen atom is chiral. The inversion is precluded if the nitrogen is coordinated to the metal. A common feature of cyclen-based macrocyclic Gd (and other Ln ) is the formation of various isomers which display dynamic behavior (interconvert/exchange) on the NMR time scale in aqueous solution [174,175]. However, the long electronic relaxation time of Gd ion prevents the observation of the NMR spectra of its complexes and its solution structure has been inferred from the H and NMR spectra of its related Ln complexes. 

In 1984, Laniado et al. [16] reported the first in vivo use of a Gd + complex, [Gd(DTPA)], a CA that was approved for clinical application in 1988. Nowadays, complexes containing gadolinium are among the most popular CAs used regularly in Medicine, and the ligands that complex the metal ion are mainly DTPA or DOTA (l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid) derivatives. In Table 46.1, the major characteristics of several clinically approved CAs are represented. 

Technetium complexes with dtpa, dmsa, or mdp (methylene diphos-phonate) can be prepared by exchange reactions of the respective rhenium complexes with pertechnetate. Despite the complication that redox as well as substitution is involved here, rates correlate with metal-ligand bond strengths. A detailed kinetic study of these reactions would be welcome. Another type of ligand exchange reaction where kinetic studies are needed is the similar situation encountered in the preparation of technetium(III), (IV), or (V) complexes by reduction of pertechnetate with tin(II) complexes of the respective ligands. 

Chelants at concentrations of 0.1 to 0.2% improve the oxidative stabiUty through the complexation of the trace metal ions, eg, iron, which cataly2e the oxidative processes. Examples of the chelants commonly used are pentasodium diethylenetriarninepentaacetic acid (DTPA), tetrasodium ethylenediarninetetraacetic acid (EDTA), sodium etidronate (EHDP), and citric acid. Magnesium siUcate, formed in wet soap through the reaction of magnesium and siUcate ions, is another chelant commonly used in simple soap bars. 

Alkaline-earth metals are often deterruined volumetricaHy by complexometric titration at pH 10, using Eriochrome Black T as indicator. The most suitable complexing titrant for barium ion is a solution of diethylenetriaminepentaacetic acid (DTPA). Other alkaline earths, if present, are simultaneously titrated, and in the favored analytical procedure calcium and strontium are deterruined separately by atomic absorption spectrophotometry, and their values subtracted from the total to obtain the barium value. 

Metals may also be linked through an oxygen or nitrogen atom to form a stable metal complex without a carbon-metal bond. These include metal complexes of ethylenediamine tetraacetate (EDTA), diethylenetriamine pentaacetate (DTPA), or ethylenediamine tetramethylphosphonate (EDTMP). Metalloid compounds include antimonyl gluconate and bismuth salicylate. 

A more elaborate representation of an EDTA-metal complex (10.13), which gives some indication of the three-dimensional aspects of the structure, shows a complex of five five-membered rings [18]. A similar representation of a DTPA-metal complex shows a system of eight five-membered rings. 

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