Preparation and preliminary evaluation of [<Superscript>67</Superscript>Ga]-tetra phenyl porphyrin complexes as possible imaging agents

[⁶⁷Ga]labeled tetraphenyl porphyrin ([⁶⁷Ga]-TPP) was prepared using freshly prepared [⁶⁷Ga]GaCl₃ and tetraphenyl porphyrin (TPPH₂) for 30–60 min at 25 °C (radiochemical purity: >97 ± 1% ITLC, >98 ± 0.5% HPLC, specific activity: 13–14 GBq/mmol). Stability of the complex was checked in final formulation and human serum for 24 h. The partition coefficient was calculated for the compound (log P 1.89). The biodistribution of the labeled compound in vital organs of wild-type rats was studied using scarification studies and SPECT imaging up to 24 h. A detailed comparative pharmacokinetic study performed for ⁶⁷Ga cation and [⁶⁷Ga]-TPP. The complex is mostly washed out from the circulation through kidneys and can be an interesting tumor imaging/targeting agent due to low liver uptake and rapid excretion through the urinary tract.     

Autoradiolysis of the 2-deoxy-2-[<Superscript>18</Superscript>F]fluoro-D-glucose radiopharmaceutical

Summary To control virtually the toxic compounds and to improve quality control of the solution of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (2-[¹⁸F]FDG), the products of its autoradiolysis were analyzed by high-performance liquid chromatography with electrospray mass spectrometric and radiometric detectors (HPLC/MS/RAD), thin layer chromatography on TLC silica plate and HPTLC on amino modified silica plate. Except Kryptofix^™ 2.2.2, glucose and fluoride anion, no by-products and impurities were observed by LC/MS analysis of fresh 2-[¹⁸F]FDG samples. The analysis performed in the time interval of 6 to 48 hours after the end of 2-[¹⁸F]FDG synthesis indicated that the activity of the autoradiolysis products separated by HPLC did not exceed 1.3%. As the main autoradiolysis products of 3.3 ^. 10^-5 to 4.4 ^. 10^-5M 2-[¹⁸F]FDG solution of original specific activity 0.5-1.5 GBq ^. cm^-3 were established: arabinose - 2.8 μM (G= 0.07/100 eV), gluconic and glucuronic acids 1.8-0.5 μM (G =0.01-0.05/100 eV), arabinose and araburonic acids occurred under 0.5 μM concentration at residual glucose contents about 0.14 mM. Radiation chemical yields of active products were calculated from molar activity of 2-[¹⁸F]FDG and the percentage of their activity: 0.5% radiochemical yield of 2-[¹⁸F]fluoroglucuronic acid corresponds to the G = 0.004/100 eV and 0.3% yield of 2-[¹⁸F]fluorogluconic acid issues G = 0.003/100 eV.     

Preparation of <Superscript>125</Superscript>I-celecoxib with high purity as a possible tumor agent

A preparation of ¹²⁵I-celecoxib is carried out via an electrophilic substitution reaction. The reaction parameters studied were celecoxib concentration, reaction temperature, pH of the reaction mixture and kinds of oxidizing agents in order to obtain a high radiochemical yield of the ¹²⁵I-celecoxib. Using 3.7 MBq of Na¹²⁵I, 150 μg (3.9 mM (mmol/L)) of celecoxib, and 1.6 mM (mmol/L) of chloramine-T (CAT) as oxidant at pH 4 and 60 °C for 15 min a maximum radiochemical yield of ¹²⁵I-celecoxib (65%) was obtained. The labeled compound was separated and purified by means of high pressure liquid chromatography (HPLC). The biological distribution in infected mice indicates the suitability of radioiodinated celecoxib as imaging of tumor.     

<Superscript>18</Superscript>F- and <Superscript>11</Superscript>C-labelling of quantum dots with n.c.a. [<Superscript>18</Superscript>F]fluoroethyltosylate and [<Superscript>11</Superscript>C]methyliodide: a feasibility study

Quantum dots functionalized on the outer surface with either amino- or carboxyl functions were labelled with [¹⁸F]fluoroethyltosylate and [¹¹C]methyliodide in order to use the positron emitter-labelled fluorescence agents for multimodality imaging techniques, i.e. fluorescence imaging and positron emission tomography. ¹⁸F-Labelling of both compounds was realized with yields up to 5% as determined by size exclusion chromatography, which is twice as much as reported in literature before [1]. ¹¹C-Labelling of amino- and carboxyl-QDs proceeded with good yields (up to 45 and 35%, respectively) under optimized reaction conditions. In general for both QD-types and both labelling agents the labelling yield increased with the amount of QDs used in the reaction as well as with reaction time and reaction temperature.     

One-step conjugation of glycylglycine with [<Superscript>18</Superscript>F]FDG and a pilot PET imaging study

This study describes a single step conjugation of Glycylglycine (GlyGly) which is a small peptide, with [¹⁸F]FDG via oxime formation. Amiooxy-functionalization of GlyGly (AO-GlyGly) was accomplished through the reaction of Boc-aminooxy succinimide ester. Conjugation reaction was performed at 100 °C for 30 min in a vial containing AO-GlyGly and [¹⁸F]FDG solution. The radiolabeled product ([¹⁸F]FDG-GlyGly) was obtained with 98.65?±?0.35% yield without any purification step which makes this method more attractive for ¹⁸F radiolabeling. The present study is concluded with an in vivo pilot animal PET study to assess biodistribution and kinetics of chemoselectively [¹⁸F]FDG tagged GlyGly in vivo.     

Synthesis of [<Superscript>14</Superscript>C] quincetone

Summary The water-soluble fullerene derivative C₆₀(OH)_x was radiolabeled with ⁶⁷GaCl₃. The labeling yields were determined by radio-PLC. The effects of pH, reaction time, temperature and the amount of C₆₀(OH)_x on the labeling yields were studied. The stability of ⁶⁷Ga-C₆₀(OH)_x was also examined. The results showed that the labeling yields could reach 97% under the best labeling conditions and the radiochemical purity of ⁶⁷Ga-C₆₀(OH)_x solution kept at 37 °C remained at 88% after 212 hours. The biodistribution studies of ⁶⁷Ga-C₆₀(OH)_x in mice showed a high localization of ⁶⁷Ga-C₆₀(OH)_x in the bone marrow, bone, liver and spleen with slow clearance and a negligible accumulation in the blood. These data suggest that the water-soluble C₆₀(OH)_x, having the same properties as microcolloids, may be used as a carrier of drug system for lymphatic targeting.     

Reduction of <Superscript>68</Superscript>Ge activity containing liquid waste from <Superscript>68</Superscript>Ga PET chemistry in nuclear medicine and radiopharmacy by solidification

PET with ⁶⁸Ga from the TiO₂- or SnO₂- based ⁶⁸Ge/⁶⁸Ga generators is of increasing interest for PET imaging in nuclear medicine. In general, radionuclidic purity (⁶⁸Ge vs. ⁶⁸Ga activity) of the eluate of these generators varies between 0.01 and 0.001%. Liquid waste containing low amounts of ⁶⁸Ge activity is produced by eluting the ⁶⁸Ge/⁶⁸Ga generators and residues from PET chemistry. Since clearance level of ⁶⁸Ge activity in waste may not exceed 10 Bq/g, as stated by European Directive 96/29/EURATOM, our purpose was to reduce ⁶⁸Ge activity in solution from >10 kBq/g to <10 Bq/g; which implies the solution can be discarded as regular waste. Most efficient method to reduce the ⁶⁸Ge activity is by sorption of TiO₂ or Fe₂O₃ and subsequent centrifugation. The required 10 Bq per mL level of ⁶⁸Ge activity in waste was reached by Fe₂O₃ logarithmically, whereas with TiO₂ asymptotically. The procedure with Fe₂O₃ eliminates ≥90% of the ⁶⁸Ge activity per treatment. Eventually, to simplify the processing a recirculation system was used to investigate ⁶⁸Ge activity sorption on TiO₂, Fe₂O₃ or Zeolite. Zeolite was introduced for its high sorption at low pH, therefore ⁶⁸Ge activity containing waste could directly be used without further interventions. ⁶⁸Ge activity containing liquid waste at different HCl concentrations (0.05–1.0 M HCl), was recirculated at 1 mL/min. With Zeolite in the recirculation system, ⁶⁸Ge activity showed highest sorption.     

Preparation and evaluation of [<Superscript>201</Superscript>Tl](III)-DTPA complex for cell labeling

Due to interesting physical properties and wide availability of ²⁰¹Tl as a SPECT radionuclide, the incorporation of this nuclide into DTPA for cell labeling was targeted. Thallium-201 (T _1/2 = 3.04 d) in Tl⁺ form was converted to Tl³⁺ cation in the presence of O₃/6M HCl and di-isopropyl ether, controlled by RTLC/gel electrophoresis methods. The final evaporated activity reacted with cDTPA in normal saline to yield [²⁰¹Tl](III)DTPA at room temperature after 0.5 hour, followed by solid phase extraction purification using C₁₈ Sep-Pak column (radiochemical yield >95%). Radiochemical purity of more than 99% was obtained using RTLC with specific activity of about 260 GBq/mmol. The stability of the tracer was checked in the final product in the presence of human serum at 37 °C up to 3 days. The partition coefficient was also measured. The labeled compound was used in red blood cell (RBC) labeling. The cell uptake ratio was determined at 4, 25 and 37 °C up to 3 hours.     

Synthesis and biodistribution of the <Superscript>99m</Superscript>Tc(CO)<Subscript>3</Subscript>-DEDT complex as a potential new radiopharmaceutical for brain imaging

The ^99mTc(CO)₃(H₂O)-DEDT complex was prepared by a two-step procedure involving the preparation of the precursor fac-[^99mTc(CO)₃(H₂O)₃]⁺, followed by the addition of sodium salt of diethyl dithiocarbamate (DEDT). The radiochemical purity (RCP) of the product was over 90% as measured by thin layer chromatography (TLC). No decomposition of the complex at room temperature was observed over a period of 6 hours. Its partition coefficient indicated that it was a lipophilic complex. The electrophoresis results showed the complex was neutral. Biodistribution in mice demonstrated that the complex can penetrate the intact blood-brain barrier (BBB) and the brain uptake (ID%/g) was 4.22 at 5-minute post-injection, suggesting the complex may lead to a further development of the radiopharma ceutical as a brain perfusion tracer.     

Preparation of <Superscript>26</Superscript>Al, <Superscript>59</Superscript>Ni, <Superscript>44</Superscript>Ti, <Superscript>53</Superscript>Mn and <Superscript>60</Superscript>Fe from a proton irradiated copper beam dump

The station for pions cancer therapy was operated at PSI from 1980 to 1992. After a cooling time of 12 years it’s made of copper beam dump was cut and samples were taken for analytical purposes. The sampling collected about 500 g of high active copper chips that can be used for separation of exotic radionuclides. The analyses by gamma spectrometry, LSC and AMS showed main nuclides present to be ⁶⁰Co, ⁵⁴Mn, ²²Na, ⁶⁵Zn, ²⁶Al, ⁵³Mn, ⁵⁹Ni, ⁶³Ni, ⁵⁵Fe and ⁶⁰Fe and ⁴⁴Ti with a daughter nuclide ⁴⁴Sc. In the frame of ERAWAST project a procedure combining selective precipitation and ion exchange for the separation of the rare radionuclides from the copper beam dump was developed. The proposed separation procedure is easy for remote controlled implementation in a hot cell. The ion exchange separation of Ni, Al, Mg, Ti and Fe was complete and high decontamination factors for copper and cobalt were achieved. Based on the developed procedure a remotely controlled system for separation of exotic radionuclides from the copper chips was set up. The full scale system was installed in a hot cell where high activity levels can be handled. In order to evaluate the reliability and functionality of the system extensive tests have been done. During the test period 13.86 g in total of the proton irradiated copper beam dump were processed for separation of ²⁶Al, ⁵⁹Ni, ⁵³Mn, ⁴⁴Ti and ⁶⁰Fe. The results showed that the system was operational and the radionuclide separation was selective with high chemical yield. The procedure manages as well the generated liquid wastes containing high level of ⁶⁰Co activity.     

Preparation and biodistribution of [<Superscript>131</Superscript>I]linezolid in animal model infection and inflammation

Linezolid is the first of new class of antibiotics, the oxazolidinones, and exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae. Aim of the study: Linezolid was to label with I-131 and potential of the radiolabeled antibiotic was to investigate in inflamed rats with S. aureus (S. aureus) and sterile inflamed rats with turpentine oil. Linezolid was labeled with I-131 by iodogen method. Biodistribution of [¹³¹I]linezolid was carried out in bacterial inflamed and sterile inflamed rats. Radiolabeling yield of [¹³¹I]linezolid was determined as 85 ± 1% at pH 2. After injecting of [¹³¹I]linezolid into bacterial inflamed and sterile inflamed rats, radiolabeled linezolid was rapidly removed from the circulation via the kidneys. Binding of [¹³¹I]linezolid to bacterial inflamed muscle (T/NT = 77.48 at 30 min) was five times higher than binding to sterile inflamed muscle (T/NT = 14.87 at 30 min) of rats. [¹³¹I]linezolid showed good localization in bacterial inflamed tissue. It was demonstrated that [¹³¹I]linezolid can be used to detect S. aureus inflammation in rats.     

Synthesis of <Superscript>14</Superscript>C analogue of 1,2-diaryl-[2-<Superscript>14</Superscript>C]-pyrroles

Three 1,2-diaryl pyrroles selective COX-2 inhibitors, 2-(4-fluorophenyl)-5-methyl-1-(4-methylsulfonyl-phenyl)-1H pyrrole, 2-(4-fluorophenyl)-1-[4-(methylsulfonyl) phenyl]-1H-pyrrole and 4-[2-(4-fluorophenyl)-1H-pyrrol-1-yl]benzenesulfon-amide, all three labeled with ¹⁴C in the 2-position were prepared from para-fluoro-benzaldehyde-[carbonyl-¹⁴C].     

Preparation of <Superscript>166</Superscript>Dy/<Superscript>166</Superscript>Ho-chitosan as an in vivo generator for radiosynovectomy

¹⁶⁶Ho is one of the most effective radionuclides used for radiosynovectomy. One method to deliver this radioisotope to target tissue is via the ¹⁶⁶Dy/¹⁶⁶Ho in vivo generator system. The aim of this work was to prepare ¹⁶⁶Dy/¹⁶⁶Ho-chitosan (¹⁶⁶Dy/¹⁶⁶Ho-CHIT) in vivo generator for radiosynovectomy applications. ¹⁶⁶Dy obtained by the irradiation of natural ¹⁶⁴Dy target. ¹⁶⁶Dy was separated from ¹⁶⁶Ho by extraction chromatographic method (separation yield; 93% and separation factor;1.7). Chitosan labeling was performed in acetic acid with 99.3 ± 0.6% radiochemical purity. Biodistribution studies on intraarticular injected rats demonstrated high retention in the knee joint even 7 days showing no radioactivity leakage from the injection site into other organs as well as any translocation of the daughter nucleus after β^? decay of ¹⁶⁶Dy.     

Functionalization of one or two methyl groups in the [Cp*<Subscript>2</Subscript>RuBr]<Superscript>+</Superscript>Br<Superscript>−</Superscript> complex in the reaction with bromine

The reaction of [Cp*₂RuBr]⁺Br⁻ with bromine in CH₂Cl₂ (CD₂Cl₂) in an inert atmosphere at room temperature produces the complexes [Cp*Ru(Br)C₅Me₄CH₂Br]⁺Br₃ ⁻ (syn conformer), [Cp*Ru(Br)C₅Me₃(CH₂Br)₂]⁺ (syn and anti conformers), and [Ru(Br)(C₅Me₄CH₂Br)₂]⁺ (syn conformer). All complexes were characterized by ¹H and ¹³C NMR spectroscopy; the former complex, by elemental analysis. These complexes were also prepared by the reaction of [Cp*RuC₅Me₄CH₂]⁺BF₄ ⁻ with bromine in CH₂Cl₂. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2712–2718, December, 2005.     

A facile preparation of ammonium [<Superscript>14</Superscript>C]thiocyanate

Summary An attractive and simple method has been developed for the preparation of ammonium [¹⁴C]thiocyanate from [¹⁴C]thiourea which eliminates the necessity of handling highly hazardous potassium [¹⁴C] cyanide. [¹⁴C]thiourea was isomerized to ammonium [¹⁴C]thiocyanate by heating the aqueous solution of thiourea (12%) in a sealed tube at 160 °C for 24 hours. The product formed was purified by silica-gel column chromatography. A radiochemical yield of 92.7% was obtained based on [¹⁴C]thiourea. The specific activity of the product obtained was 53.3 mCi/mmol (1.97 GBq/mmol) and the radiochemical purity was greater than 99%. This method has not been reported so far for the production of this labeled compound.     

Hydrogenolysis of 7-phenyltricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptan-1-carboxylic acid. Synthesis of ketones with tricyclo[4.4.0.0<Superscript>2,7</Superscript>]decane and tricyclo[5.4.0.0<Superscript>2,8</Superscript>]undecane skeletons

Hydrogenation of 7-phenyltricyclo[4.1.0.0^2,7]heptane-1-carboxylic acid over Raney nickel occurred in the syn-stereoselective fashion to give anti-7-phenylbicyclo[3.1.1]heptane-exo-6-carboxylic acid. The latter was used to synthesize 4,5-benzotricyclo[4.4.0.0^2,7]dec-4-en-3-one and two isomeric higher homologs, 5,6-benzotricyclo[5.4.0.0^2,8]undec-5-en-3-and-4-ones.     

Quantum chemical analysis of possible fragmentation of [M + H]<Superscript>+</Superscript> and [M + Na]<Superscript>+</Superscript> complexes of monosubstituted methane,cyclohexane, and benzene derivatives in mass spectrometric studies

The formation and fragmentation energies of the proton and sodium cation complexes with monosubstituted methane, cyclohexane, and benzene derivatives in which carbon atoms are bonded to substituents (NH₂, OH, F, Cl, Br, ONO₂, NO₂, COOH, CN, and Ph) were calculated by the B3LYP/6-31G(d) method. For [M + Na]⁺ complexes, the formation energies are much lower (and differ from one another to a much lesser extent), while the dissociation energies are much higher, than the corresponding energies of the [M + H]⁺ complexes. Na⁺ cation shows a lower selectivity toward localization at functional groups in molecules compared to H⁺. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 246–249, February, 2008.     

<Superscript>234</Superscript>U/<Superscript>235</Superscript>U activity ratios as a probe for the <Superscript>238</Superscript>U/<Superscript>235</Superscript>U half-life ratio

High-resolution alpha-particle spectrometry was performed on three uranium materials enriched in ²³⁵U. Besides the ²³⁵U peaks, separate peaks belonging to impurity traces of ²³⁴U could be quantified. Relying on the isotopic composition of the uranium, as determined by mass spectrometry, the ratio of the half-lives of ²³⁸U and ²³⁵U was determined via the activity ratio of ²³⁴U and ²³⁵U in the materials. As an intermediate link, the ²³⁴U/²³⁸U half-life ratio was taken from published mass spectrometric analyses of ‘secular equilibrium’ uranium material. The resulting half-life ratio T _1/2(²³⁸U)/T _1/2(²³⁵U) = 6.351±0.031 is in agreement with the commonly adopted half-life values determined by Jaffey et al.