24 research outputs found
Abstracts from the 11th Symposium on Experimental Rhinology and Immunology of the Nose (SERIN 2017)
Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation Part I. Multi-column chromatographic process for clinically applicable
The conventional multi-column solid phase extraction (SPE) chromatography technique using di-(2-ethylhexyl)orthophosphoric acid (HDEHP) impregnated OASIS-HLB sorbent based SPE resins (OASIS-HDEHP) was developed for the separation of no-carrier added (n.c.a) Lu-177 from the bulk quantity of ytterbium target. This technique exploited the large variation of lutetium metal ion distribution coefficients in the varying acidity of the HCl solution-OASIS-HDEHP resin systems for the consecutive loading-eluting cycles performed on different columns. The production batches of several hundred mCi n.c.a Lu-177 radioisotope separated from 50 mg Yb target activated in a nuclear reactor of medium neutron nux (Phi = 5 center dot 10(13) n.cm(-2).s(-1)) were successfully performed using the above mentioned separation technique. With the target irradiation in a reactor of thermal neutron flux Phi = 2 center dot 10(14) n.cm(-2).s(-1) or the parallel run of several separation units, many Ci-s of n.c.a Lu-177 can be profitably produced. The OASIS-HDEHP resin based multi-column SPE chromatography technique makes the separation process simple and economic and offers an automation capability for operation in highly radioactive hazardous environments. © 2008, Springer
Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation Part II. The conventional column chromatographic separation combined with HPLC for high purity
HPLC technique combined with the simple conventional column solid phase extraction (SPE) chromatography using di-(2-
ethylhexyl)orthophosphoric acid (HDEHP) impregnated OASIS-HLB sorbent based SPE resins (OASIS-HDEHP ) was developed for the
separation of no-carrier added (n.c.a) 177Lu from the bulk quantity of ytterbium target. This combination strategy was based on combining the
advantages of the better resolution of HPLC separation of n.c.a 177Lu from the few milligram level Yb target with the high capacity of the OASISHDEHP
column for the separation of 177Lu from the bulk Yb target. The production batches of several hundred mCi activity of n.c.a 177Lu
radioisotope separated from 50 mg Yb target activated in a nuclear reactor of medium neutron flux (Φ = 5.1013 n.cm–2.s–1) were successfully
performed using this combined separation technique. With the target irradiation in a reactor of higher thermal neutron flux or with the parallel run of several separation units, several Ci-s of n.c.a 177Lu can be profitably produced on a commercial production basis. © 2008, Springer
Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque
Alzheimer's disease (AD) and related dementias show increasing clinical prevalence, yet our understanding of the etiology and pathobiology of disease-related neurodegeneration remains limited. In this regard, noninvasive imaging with radiotracers for positron emission tomography (PET) presents a unique tool for quantifying spatial and temporal changes in characteristic biological markers of brain disease and for assessing potential drug efficacy. PET radiotracers targeting different protein markers are being developed to address questions pertaining to the molecular and/or genetic heterogeneity of AD and related dementias. For example, radiotracers including [11C]-PiB and [18F]-AV-45 (Florbetapir) are being used to measure the density of Aβ-plaques in AD patients and to interrogate the biological mechanisms of disease initiation and progression. Our focus is on the development of novel PET imaging agents, targeting proteins beyond Aβ-plaques, which can be used to investigate the broader mechanism of AD pathogenesis. Here, we present the chemical basis of various radiotracers which show promise in preclinical or clinical studies for use in evaluating the phenotypic or biochemical characteristics of AD. Radiotracers for PET imaging neuroinflammation, metal ion association with Aβ-plaques, tau protein, cholinergic and cannabinoid receptors, and enzymes including glycogen-synthase kinase-3β and monoamine oxidase B amongst others, and their connection to AD are highlighted. Copyright © 2013 John Wiley & Sons, Ltd
Influence of metal ions on the Ga-68-labeling of dotatate
The influence of metal cations (Fe3+, Fe2+, In3+, Cu2+, Ca2+, Al3+, Co2+, Lu3+, Ni2+, Pb2+, Ti4+, Y3+, Yb3+, Zn2+, and Zr4+) on the radiolabeling yield of [68Ga(DOTATATE)] was evaluated. Our most important observation was that, within our experimental limit, the metal ion/ligand ratio plays a critical role on the influence of most metal ions. More in-depth studies, with Cu2+ and Fe3+, revealed that reaction temperature and concentration changes have little effect, but speciation changes with pH are crucial. Furthermore, we found that [68Ga(DOTATATE)] is stable in the presence of high concentrations of Fe3+, Zn2+ and Pb2+, but transmetalates with Cu2+ at 95 °C. © 2013, Elsevier Ltd
A tunable one-pot three-component synthesis of an125I and Gd-labelled star polymer nanoparticle for hybrid imaging with MRI and nuclear medicine
The successful treatment of a disease via individualized treatment protocols relies on an early and accurate diagnosis. Advances to imaging hardware, such as hybrid PET/MRI scanners, have overcome the inherit disadvantages associated with the individual imaging modality. However, well-designed multimodal contrast agents are essential to optimally exploit hybrid PET/MRI systems. Herein, we show that core-cross-linked azide-functional star polymer nanoparticles can be simultaneously labelled with a radioisotope (radioiodine) and a clinically-used MRI contrast agent (Gd-DOTA) by exploiting an elegant copper-catalyzed one-pot three-component reaction creating an iodotriazole. The nanoparticles have a longitudinal relaxivity of 5.7 mM(-1) s(-1) at 7 T (as compared to 3.8 mM(-1) s(-1) for commercially available Gd-DTPA), and a radiochemical yield of 58% was achieved. Furthermore, we show that the radioiodine content can be fine-tuned without affecting the final Gd-DOTA loading. While we have demonstrated the versatility of the approach with I-125, an isotope widely used in biological research, the availability of various radioiodine isotopes enables potential applications in SPECT (I-123), PET (I-124) and in theranostics by combining radioimmunotherapy (I-131) with MRI
Alternative chromatographic processes for no-carrier added 177Lu radioisotope separation
Selective targeting of melanoma using N-(2-diethylaminoethyl) 4-[18F]fluoroethoxy benzamide (4-[18F]FEBZA): a novel PET imaging probe
Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation
Electrochemiluminescent monomers for solid support syntheses of Ru(II) PNA bioconjugates - multimodal biosensing tools with enhanced duplex stability
The feasibility of devising a solid support mediated approach to multimodal Ru(II)-peptide nucleic acid (PNA) oligomers is explored. Three Ru(II)-PNA-like monomers, [Ru(bpy)(2)(Cpp-L-PNA-OH)](2+) (M1), [Ru(phen)(2)(Cpp-L-PNA-OH)](2+) (M2), and [Ru(dppz)(2)(Cpp-L-PNA-OH)](2+) (M3) (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine, Cpp-L-PNA-OH = [2-(N-9-fluorenylmethoxycarbonyl)aminoethyl]-N-[6-(2-(pyridin-2yl)pyrimidine-4-carboxamido)hexanoyl]-glycine), have been synthesized as building blocks for Ru(II)-PNA oligomers and characterized by IR and (1)H NMR spectroscopy, mass spectrometry, electrochemistry and elemental analysis. As a proof of principle, M1 was incorporated on the solid phase within the PNA sequences H-g-c-a-a-t-a-a-a-a-Lys-NH(2) (PNA1) and H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-lys-NH(2) (PNA4) to give PNA2 (H-g-c-a-a-t-a-a-a-a-M1-lys-NH(2)) and PNA3 (H-P-K-K-K-R-K-V-g-c-a-a-t-a-a-a-a-M1-lys-NH(2)), respectively. The two Ru(II)-PNA oligomers, PNA2 and PNA3, displayed a metal to ligand charge transfer (MLCT) transition band centered around 445 nm and an emission maximum at about 680 nm following 450 nm excitation in aqueous solutions (10 mM PBS, pH 7.4). The absorption and emission response of the duplexes formed with the cDNA strand (DNA: 5'-T-T-T-T-T-T-T-A-T-T-G-C-T-T-T-3') showed no major variations, suggesting that the electronic properties of the Ru(II) complexes are largely unaffected by hybridization. The thermal stability of the PNA·DNA duplexes, as evaluated from UV melting experiments, is enhanced compared to the corresponding nonmetalated duplexes. The melting temperature (T(m)) was almost 8 °C higher for PNA2·DNA duplex, and 4 °C for PNA3·DNA duplex, with the stabilization attributed to the electrostatic interaction between the cationic residues (Ru(II) unit and positively charged lysine/arginine) and the polyanionic DNA backbone. In presence of tripropylamine (TPA) as co-reactant, PNA2, PNA3, PNA2·DNA and PNA3·DNA displayed strong electrochemiluminescence (ECL) signals even at submicromolar concentrations. Importantly, the combination of spectrochemical, thermal and ECL properties possessed by the Ru(II)-PNA sequences offer an elegant approach for the design of highly sensitive multimodal biosensing tools