A Fluorine-18 Radiolabeling Method Enabled by Rhenium(I) Complexation Circumvents the Requirement of Anhydrous Conditions

Azeotropic distillation is typically required to achieve fluorine-18 radiolabeling during the production of positron emission tomography (PET) imaging agents. However, this time-consuming process also limits fluorine-18 incorporation, due to radioactive decay of the isotope and its adsorption to the drying vessel. In addressing these limitations, the fluorine-18 radiolabeling of one model rhenium(I) complex is reported here, which is significantly improved under conditions that do not require azeotropic drying. This work could open a route towards the investigation of a simplified metal-mediated late-stage radiofluorination method, which would expand upon the accessibility of new PET and PET-optical probes

Tunable and noncytotoxic PET/SPECT-MRI multimodality imaging probes using colloidally stable ligand-free superparamagnetic iron oxide nanoparticles

Physiologically stable multimodality imaging probes for positron emission tomography/single-photon emission computed tomography (PET/SPECT)-magnetic resonance imaging (MRI) were synthesized using the superparamagnetic maghemite iron oxide (γ-Fe2O3) nanoparticles (SPIONs). The SPIONs were sterically stabilized with a finely tuned mixture of diblock copolymers with either methoxypolyethylene glycol (MPEG) or primary amine NH2 end groups. The radioisotope for PET or SPECT imaging was incorporated with the SPIONs at high temperature. 57Co2+ ions with a long half-life of 270.9 days were used as a model for the radiotracer to study the kinetics of radiolabeling, characterization, and the stability of the radiolabeled SPIONs. Radioactive 67Ga3+ and Cu2+-labeled SPIONs were also produced successfully using the optimized conditions from the 57Co2+-labeling process. No free radioisotopes were detected in the aqueous phase for the radiolabeled SPIONs 1 week after dispersion in phosphate-buffered saline (PBS). All labeled SPIONs were not only well dispersed and stable under physiological conditions but also noncytotoxic in vitro. The ability to design and produce physiologically stable radiolabeled magnetic nanoparticles with a finely controlled number of functionalizable end groups on the SPIONs enables the generation of a desirable and biologically compatible multimodality PET/SPECT-MRI agent on a single T2 contrast MRI probe. © 2017 Dove Press Ltd.This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License

Synthesis and biological characterisation of 18F-SIG343 and 18F-SIG353, novel and high selectivity σ2 radiotracers, for tumour imaging properties

Sigma2 (σ2) receptors are highly expressed in cancer cell lines and in tumours. Two novel selective 18F-phthalimido σ2 ligands, 18F-SIG343 and 18F-SIG353, were prepared and characterised for their potential tumour imaging properties. © 2013 Nguyen et al.; licensee Springer.© Nguyen et al.; licensee Springer. 2013 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Evaluation of radioisotope quality aspects for preparation of high specific activity [Ga-68]-NOTA-AnnexinA1.

The bi-functional chelator NOTA-(p-Bn)-NCS permits radio-labelling heat sensitive proteins with Ga-68 (t1/2=68 min) for positron emission tomography. Complexation at room temperature (RT) completes within minutes and in vivo transmetalation is negligible. Here, influences of trace metal cations, on radiochemical yield (RCY) and specific radioactivity (SRA) are assessed. Conjugation of NOTA-(p-Bn)-NCS to AnnexinA1 was performed at varying stoichiometries and conjugates purified by size exclusion high-performance liquid chromatography. Available complexation sites per protein were identified by colorimetric assay and titration with carrier added Ga-67. The complexation of Ga-68 by NOTA-AnnexinA1 at RT and 37°C was systematically studied with and without addition of competing trace metal cations. Ga-67 was used for confirmation of observed trends. Integrity of the radio-conjugate was assessed by addition of up to 104 fold excess of metal cations or apo-transferin and exposure to human serum at 37°C. Gallium-68 gave RCY of N99% within minutes at RT whereas, Ga-67 yielded max 85% dropping as the stock decayed. Presence of Fe(III) showed significant influence on RCY. Once formed, the radio-conjugate showed negligible loss of radioactivity under even the most extreme conditions investigated. SRA and RCY of the radio-conjugate depend significantly on absence of particularly Fe(III) during complexation

Rhenium and technetium tricarbonyl complexes of N-Heterocyclic carbene ligands

A strategy for the conjugation of N-heterocyclic carbene (NHC) ligands to biomolecules via amide bond formation is described. Both 1-(2-pyridyl)imidazolium or 1-(2-pyridyl)benzimidazolium salts functionalized with a pendant carboxylic acid group were prepared and coupled to glycine benzyl ester using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. A series of 10 rhenium(I) tricarbonyl complexes of the form [ReX(CO)3(ĈN)] (ĈN is a bidentate NHC ligand, and X is a monodentate anionic ligand: Cl–, RCO2–) were synthesized via a Ag2O transmetalation protocol from the Re(I) precursor compound Re(CO)5Cl. The synthesized azolium salts and Re(I) complexes were characterized by elemental analysis and by 1H and 13C NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re(I) complexes were determined by single-crystal X-ray diffraction. 1H NMR and mass spectrometry studies for an acetonitrile-d3 solution of [ReCl(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)] show that the monodentate chloride ligand is labile and exchanges with this solvent yielding a cationic acetonitrile adduct. For the first time the labeling of an NHC ligand with technetium-99m is reported. Rapid Tc-99m labeling was achieved by heating the imidazolium salt 1-(2-pyridyl)-3-methylimidazolium iodide and Ag2O in methanol, followed by the addition of fac-[99mTc(OH2)3(CO)3]+. To confirm the structure of the 99mTc-labeled complex, the equivalent 99Tc complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [99m/99Tc(CH3CN)(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)]+ with an acetonitrile molecule coordinated to the metal center. © 2014 American Chemical Societ

Radiochemical separation and quality assessment for the 68Zn target based 64Cu radioisotope production

The radiochemical separation of the different radionuclides (64Cu, 67Cu, 67Ga, 66Ga, 56Ni, 57Ni, 55Co, 56Co, 57Co, 65Zn, 196Au ) induced in the Ni supported Cu substrate – 68Zn target system, which was bombarded with the 29.0 MeV proton beam, was performed by ion-exchange chromatography using successive isocratic and/or concentration gradient elution techniques. The overlapped gamma-ray spectrum analysis method was developed to assess the 67Ga and 67Cu content in the 64Cu product and even in the post-67Ga production 68Zn target solution without the support of radiochemical separation. This method was used for the assessment of 64+67Cu radioisotope separation from 67Ga , the quality control of 64Cu product and the determination of the 68Zn (p,2p)67Cu reaction yield. The improvement in the targetry and the optimization of proton beam energy for the 68Zn target based 64Cu and 67Ga production were proposed based on the stopping power and range of the incident proton and on the excitation functions, reaction yields and different radionuclides induced in the target system. © 2008, Springer

Clusterin facilitates in vivo clearance of extracellular misfolded proteins

The extracellular deposition of misfolded proteins is a characteristic of many debilitating age-related disorders. However, little is known about the specific mechanisms that act to suppress this process in vivo. Clusterin (CLU) is an extracellular chaperone that forms stable and soluble complexes with misfolded client proteins. Here we explore the fate of complexes formed between CLU and misfolded proteins both in vitro and in a living organism. We show that proteins injected into rats are cleared more rapidly from circulation when complexed with CLU as a result of their more efficient localisation to the liver and that this clearance is delayed by pre-injection with the scavenger receptor inhibitor fucoidan. The CLU-client complexes were found to bind preferentially, in a fucoidan-inhibitable manner, to human peripheral blood monocytes and isolated rat hepatocytes and in the latter cell type were internalized and targeted to lysosomes for degradation. The data suggest, therefore, that CLU plays a key role in an extracellular proteostasis system that recognises, keeps soluble, and then rapidly mediates the disposal of misfolded proteins

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