@article {RADCHENKO2014721,
	title = {Desferrioxamine as an appropriate chelator for 90Nb: Comparison of its complexation properties for M-Df-Octreotide (M=Nb, Fe, Ga, Zr)},
	journal = {Nuclear Medicine and Biology},
	volume = {41},
	number = {9},
	year = {2014},
	pages = {721 - 727},
	abstract = {The niobium-90 radioisotope (90Nb) holds considerable promise for use in immuno-PET, due to its decay parameters (t{\textonehalf}=14.6h, positron yield=53\%, E{\ss}+mean=0.35MeV and E{\ss}+max = 1.5MeV). In particular, 90Nb appears well suited to detect in vivo the pharmacokinetics of large targeting vectors (50{\textendash}150kDa). In order to be useful for immuno-PET chelators are required to both stabilize the radionuclide in terms of coordination chemistry and to facilitate the covalent attachment to the targeting vector. Different chelators were evaluated for this purpose in terms of radiolabelling efficiency and stability of the radiolabelled Nb(V) complex and in order to determine the most suitable candidate for conjugation to a biologically relevant targeting vector. For the purpose of studying the complexation properties the niobium radioisotope 95Nb was used as an analogue of 90Nb, by virtue of its longer half-life (35days) and lower cost (reactor-based production). Acyclic and cyclic chelators were investigated, with desferroxamine [Df: (N{\textquoteright}-{5-[acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl) (hydroxy)amino]-4-oxobutanoyl} amino)pentyl]-N-hydroxysuccinamide)] emerging as the best candidate. Greater than 99\% radiolabelling was achieved at room temperature over a wide pH range. The 95Nb-Df complex is sufficiently stable for immuno-PET (<7\% degradation over 7days in vitro). As a proof-of-principle, a Df conjugate featuring a well-established targeting vector, (D)-Phe1-octreotide, was evaluated. The fast labelling kinetics of the unconjugated chelator (Df) were retained for Df-succinyl-(D)Phe1-octreotide (Df-OC), with>90\% labelling after 1h at room temperature over the pH range 5{\textendash}7. Stability studies, performed in vitro in serum at physiological temperature (37{\textdegree}C), revealed that 87{\textpm}2\% of the radiolabelled molecule remained intact after 7days. Competition studies with relevant metal ions (zirconium(IV), gallium(III) and iron(III)) have been performed with Df-OC to gain insight to the relative stability [Nb-Df]-OC complex to transmetallation. At equimolar metal ion concentrations the [Nb-Df]-OC complex showed the greatest overall stability. The favourable radiolabelling characteristics of Df-OC and its stability indicate that Df is a potentially very useful chelator for the development of radiopharmaceuticals for 90Nb-PET.},
	keywords = {Chelators, DESFERRIOXAMINE, Df-Octereotide, Positron emitter Nb, STABILITY},
	issn = {0969-8051},
	doi = {https://doi.org/10.1016/j.nucmedbio.2014.06.006},
	url = {http://www.sciencedirect.com/science/article/pii/S0969805114004387},
	author = {Valery Radchenko and Stefan Busse and Frank Roesch}
}
@article {4199,
	title = {Active oxygen species formation in synaptosomes exposed to an aluminum chelator},
	journal = {Neurotoxicology and Teratology},
	volume = {20},
	number = {3},
	year = {1998},
	note = {ISI Document Delivery No.: ZU241Times Cited: 4Cited Reference Count: 37},
	month = {May-Jun},
	pages = {317-320},
	type = {Article},
	abstract = {This study evaluates the potential of two chelators, 1,2-dimethyl-3-hydroxypyridine-4-one (Hdpp) and 1-n-butyl-2-methyl-3-hydroxypyridin-4-one (Hnbp), to modulate cerebral rates of free radical production. The fluorometric assay for 2{\textquoteright},7{\textquoteright}-dichlorofluorescein, which is formed by oxidation of a nonfluorescent precursor (2{\textquoteright},7{\textquoteright}-dichlorofluorescin diacetate), was used to assay reactive oxygen species (ROS) production. The chelator Hdpp alone and the aluminum complexes of each chelator, Al(dpp)(3) and Al(nbp)(3), all inhibited basal rates of generation of ROS within a rat cerebral synaptosomal fraction. In the presence of an iron salt (1 mu M FeSO4), a major enhancement of syn aptosomal ROS formation was apparent. However, with the addition of an equimolar concentration of Hdpp, Al(dpp)(3), or Al(nbp)(3), this stimulation was completely abolished. The N-substituted-3-hydroxy-4-pyridinones have been proposed to be of clinical utility for the removal of iron or aluminum from tissues. The clinical potential of this class of chelator may be enhanced by their ability to inhibit iron-related oxidative events. (C) 1998 Elsevier Science Inc.},
	keywords = {3-HYDROXY-4-PYRIDINONES, aluminum, ALZHEIMERS-DISEASE, CHELATOR, COMPLEXES, DEFEROXAMINE, DESFERRIOXAMINE, Free Radicals, hydroxypyridinones, iron, LIPID-PEROXIDATION, metal chelation, NEUROFIBRILLARY TANGLES, QUANTITATION, RATS, reactive oxygen species},
	isbn = {0892-0362},
	url = {<Go to ISI>://000074176500011},
	author = {Bondy, S. C. and Tseng, H. and Orvig, Chris}
}
@article {2952,
	title = {PHARMACOKINETICS OF ALUMINUM 3-HYDROXYPYRIDIN-4-ONE COMPLEXES - IMPLICATIONS FOR ALUMINUM REDISTRIBUTION SUBSEQUENT TO CHELATION-THERAPY},
	journal = {Toxicology},
	volume = {92},
	number = {1-3},
	year = {1994},
	note = {ISI Document Delivery No.: PK035Times Cited: 14Cited Reference Count: 34},
	month = {Sep},
	pages = {193-202},
	type = {Article},
	abstract = {The pharmacokinetics of selected aluminum-hydroxypyridinone (Al-HP) complexes were determined in rats to better understand the relationship between their disposition and elimination parameters and the safety of HPs in the chelation therapy of Al intoxication. Five complexes were administered as i.v. bolus doses of Al-HP (0.25 mmol/kg Al-0.75 mmol/kg HP). The Al-HP steady state volumes of distribution ranged from 220 to 871 ml/kg, suggesting that each complex distributed out of the vascular compartment (which should have been approximate to 65 ml/kg). Systemic clearances ranged from 189 to 906 ml/h per kg. Elimination half-lives (t(1/2)) and mean residence times ranged from 0.36 to 0.84 and 0.52 to 1.20 h, respectively. The Al-CP20 complex had a short t(1/2) and a midrange volume of distribution. It demonstrated no apparent toxicity, whereas myoclonic seizures were observed after Al-CP22, Al-CP24 and Al-CP94 administration. The most appropriate choice for Al chelation among the HPs tested may be CP20. Characterization of the distribution and elimination of Al-HP complexes improves the understanding of potential toxicity that may be associated with HP therapy of Al intoxication.},
	keywords = {3-HYDROXY-4-PYRIDINONES, 3-HYDROXYPYRIDIN-4-ONES, aluminum, ALUMINUM CHELATION, ALUMINUM TOXICITY, CHELATION, DESFERRIOXAMINE, ENCEPHALOPATHY, gallium, INTOXICATION, INVITRO, IRON CHELATORS, OCULAR TOXICITY, pharmacokinetics, RENAL-FAILURE, SUBCUTANEOUS DEFEROXAMINE},
	isbn = {0300-483X},
	url = {<Go to ISI>://A1994PK03500015},
	author = {Allen, D. D. and Orvig, Chris and Yokel, R. A.}
}
@article {7283,
	title = {COMPLEXATION OF IRON WITH THE ORALLY ACTIVE DECORPORATION DRUG-L1 (3-HYDROXY-1,2-DIMETHYL-4-PYRIDINONE)},
	journal = {Clinical Chemistry},
	volume = {38},
	number = {4},
	year = {1992},
	note = {ISI Document Delivery No.: HN921Times Cited: 18Cited Reference Count: 37},
	month = {Apr},
	pages = {562-565},
	type = {Note},
	abstract = {{The stability constants for the Fe(III) complexes of the orally active iron decorporation drug L1 (3-hydroxy-1,2-dimethyl-4-pyridinone) have been determined by potentiometric titration [glass electrode, 25.0-degrees-C},
	keywords = {2-DIMETHYL-3-HYDROXYPYRID-4-ONE L1, aluminum, CHELATOR 1, CHEMISTRY, DESFERRIOXAMINE, EQUILIBRIUM, gallium, HETEROAROMATIC CHELATORS, IRON OVERLOAD, IRON-BINDING DRUGS, LONG-TERM TRIAL, MOBILIZATION, POTENTIOMETRIC TITRATION, PROGRAM},
	isbn = {0009-9147},
	url = {<Go to ISI>://A1992HN92100022},
	author = {Kline, M. A. and Orvig, Chris}
}
