Activity standardization of Na

The activity of a ²²Na solution was measured by means of two 4πβ−γ coincidence-counting techniques. The first method corresponds to the classical 4πβ−γ coincidence counting and requires the β⁺-branching ratio. The second procedure is based on a variation of the distance between source and gamma detector. The efficiency for detecting the sum peak is then extrapolated to zero, giving the total source activity. The combination of both methods yields the β⁺ branching ratio. In addition, liquid scintillation counting using the CIEMAT/NIST-method as well as a secondary standardization by means of calibrated ionization chambers were used for activity determination. The results were checked for consistency and an ampoule was submitted to the BIPM to have the activity result entered into the database of the International Reference System (SIR).     

Half-life measurements of Rb by liquid scintillation counting

The specific activity of natural ⁸⁷Rb was measured by means of 4πβ liquid scintillation counting in a two-photomultiplier-tube spectrometer. ³H-efficiency tracing was used together with the CIEMAT/NIST method to obtain the detection efficiency. For this purpose a new parameterization of the shape factor for the third forbidden non-unique β-transition was performed. The hygroscopic behaviour of the salts used for sample preparation was studied. The half-life of ⁸⁷Rb was found to be T_1/2=4.967(32)×10¹⁰ y.     

Improved synthesis of β-CIT and [C]β-CIT labeled at nitrogen or oxygen positions

The important radiotracer precursor 2β-carbomethoxy-3β-(4-idophenyl)-tropane (β-CIT, RTI-55) was made in 52% overall yield from cocaine. Key steps were improved conjugate Grignard addition to anhydroecgonine methyl ester with >3.5:1 2β: 2-isomer selectivity, and a mild new direct aromatic iodination with I₂ and silver triflate in CH₂Cl₂. The [¹¹C]β-CIT was labeled at either the N or O positions with [¹¹C]methyl triflate; and efficient reversed-phase HPLC was used to preparatively separate [N-¹¹C]β-CIT from N-nor-β-CIT for the first time, and a fast solid-phase extraction (SPE) method was applied to preparatively separate [O-¹¹C]β-CIT from β-CIT-acid precursor.     

Purification and activity standardisation of a Ho solution

As part of a project to use the long-lived (T_1/2=1200a) ^166mHo as reference source in its reference ionisation chamber, IRA standardised a commercially acquired solution of this nuclide using the 4πβ–γ coincidence and 4πγ (NaI) methods. The ^166mHo solution supplied by Isotope Product Laboratories was measured to have about 5% Europium impurities (3% ¹⁵⁴Eu, 0.94% ¹⁵²Eu and 0.9% ¹⁵⁵Eu). Holmium had therefore to be separated from europium, and this was carried out by means of ion-exchange chromatography. The holmium fractions were collected without europium contamination: 162 h long HPGe gamma measurements indicated no europium impurity (detection limits of 0.01% for ¹⁵²Eu and ¹⁵⁴Eu, and 0.03% for ¹⁵⁵Eu). The primary measurement of the purified ^166mHo solution with the 4π (PC) β–γ coincidence technique was carried out at three gamma energy settings: a window around the 184.4 keV peak and gamma thresholds at 121.8 and 637.3 keV. The results show very good self-consistency, and the activity concentration of the solution was evaluated to be 45.640±0.098 kBq/g (0.21% with k=1). The activity concentration of this solution was also measured by integral counting with a well-type 5″×5″ NaI(Tl) detector and efficiencies computed by Monte Carlo simulations using the GEANT code. These measurements were mutually consistent, while the resulting weighted average of the 4π NaI(Tl) method was found to agree within 0.15% with the result of the 4πβ–γ coincidence technique. An ampoule of this solution and the measured value of the concentration were submitted to the BIPM as a contribution to the Système International de Référence.     

2Beta-carbomethoxy-3beta-(4- and 2-[18F]fluoromethylphenyl)tropanes: specific probes for in vivo quantification of central dopamine transporter sites

Dopamine reuptake transporter binding kinetics of 2β-carbomethoxy-3β-(4-[¹⁸F]fluoromethylphenyl)tropane (p-FWIN) and 2β-carbomethoxy-3β-(2-[¹⁸F]fluoromethylphenyl)tropane (o-FWIN) were determined in vervet monkeys using positron emission tomography (PET). Ligand localization was rapid and specific to the striatum with kinetic estimates comparable with those of ¹¹C-labeled WIN 35,428 (CWIN). Binding was more specific with p-FWIN than with CWIN or o-FWIN. The relatively longer half-life of the ¹⁸F radiolabel enabled longer acquisition times with p-FWIN, resulting in less variability in the kinetic estimates.     

Measurement of Pu γ-ray intensities between 148 and 161 keV

Utilizing Pu isotopic standards characterized by the Institute for Nuclear Materials and Measurement (IRMM), New Brunswick Laboratory (NBL) measured the γ-ray branching ratios of the 148.567-keV ²⁴¹Pu, the 152.72-keV ²³⁸Pu, the 159.995-keV ²⁴¹Pu and the 160.28-keV ²⁴⁰Pu γ-rays. The study reported here includes the measurement of four IRMM standards, utilizing three different detectors for a total of 16 spectra, finding branching ratios of (1.863 ± 0.008) × 10⁻⁶, (9.230 ± 0.068) × 10⁻⁶, (6.321 ± 0.040) × 10⁻⁸ and (4.065 ± 0.017) × 10⁻⁶, γ/disintegration, respectively.     

F-18 Polyethyleneglycol stilbenes as PET imaging agents targeting Abeta aggregates in the brain

This paper describes a novel series of ¹⁸F-labeled polyethyleneglycol (PEG)-stilbene derivatives as potential β-amyloid (Aβ) plaque-specific imaging agents for positron emission tomography (PET). In these series of compounds, ¹⁸F is linked to the stilbene through a PEG chain, of which the number of ethoxy groups ranges from 2 to 5. The purpose of adding PEG groups is to lower the lipophilicity and improve bioavailability. The syntheses of the “cold” compounds and the ¹⁸F-labeled PEG stilbene derivatives are successfully achieved. All of the fluorinated stilbenes displayed high binding affinities in an assay using postmortem AD brain homogenates (K_i=2.9–6.7 nM). Labeling was successfully performed by a substitution of the mesylate group of 10a–d by [¹⁸F]fluoride giving the target compounds [¹⁸F]12a–d (EOS, specific activity, 900–1500 Ci/mmol; radiochemical purity >99%). In vivo biodistribution of these novel ¹⁸F ligands in normal mice exhibited excellent brain penetrations and rapid washouts after an intravenous injection (6.6–8.1 and 1.2–2.6 %dose/g at 2 and 60 min, respectively). Autoradiography of postmortem AD brain sections of [¹⁸F]12a–d confirmed the specific binding related to the presence of Aβ plaques. In addition, in vivo plaque labeling can be clearly demonstrated with these ¹⁸F-labeled agents in transgenic mice (Tg2576), a useful animal model for Alzheimer's disease. In conclusion, the preliminary results strongly suggest these fluorinated PEG stilbene derivatives are suitable candidates as Aβ plaque imaging agents for studying patients with Alzheimer's disease.     

Bone powder exposed to the action of C and Mg ion beams as investigated by electron paramagnetic resonance spectroscopy

Bovine compact bone powder was irradiated with -particles of ²⁴¹Am, ¹²C⁶⁺ and ³⁵Mg¹²⁺ ion beams, then examined by the e.p.r. spectroscopy. The stable e.p.r. signal found is of the same characteristic as that observed in γ-irradiated bone (g = 2.0017, g = 1.9973, ΔH_pp = 0.85 mT). Thus, the structure of radiation induced paramagnetic center in bone does not depend on the LET of radiation used. The radiolytic yields of the formation of stable paramagnetic centres in bone powder irradiated with γ-rays are G_γ = 0.08 ± 0.01 while with ¹²C⁶⁺ ion beams roughly about G_c = 0.02, respectively.     

A liquid-scintillation-based primary standardization of Pb

A new radioactivity solution standard of ²¹⁰Pb has been developed and will be disseminated by the National Institute of Standards and Technology (NIST) as standard reference material (SRM) 4337. This new ²¹⁰Pb solution standard is contained in a 5 mL flame-sealed borosilicate glass ampoule, consists of (5.133±0.002) g of a nominal 1 mol L⁻¹ nitric acid solution, has a density of (1.028±0.002) g mL⁻¹ at 20 °C, has carrier ion concentrations of about 11 μg Pb²⁺ and 21 μg Bi³⁺ per gram of solution, and is certified to contain a massic activity (9.037±0.22) kBq g⁻¹ as of the reference time 1200 EST, 15 June 2006. All of the uncertainties cited above correspond to standard uncertainties multiplied by a coverage factor k=2. The standardization for the ²¹⁰Pb content of the solution was based on 4πβ liquid scintillation (LS) measurements using CIEMAT/NIST ³H-standard efficiency tracing (CNET). Confirmatory determinations were also performed by high-resolution HPGe γ-ray spectrometry, by 2π spectrometry with a Si surface barrier detector of separated ²¹⁰Po, and by 4πβ(LS)–γ(NaI) anticoincidence counting.     

Production of Ho through Dy(n,γ)Dy(n, γ)Dy(β)Ho and separation of Ho

After irradiation with thermal neutrons ¹⁶⁴Dy produces ¹⁶⁶Ho through the nuclear reaction: ¹⁶⁴Dy(n,γ) ¹⁶⁵Dy(n,γ) ¹⁶⁶Dy ¹⁶⁶Ho. ¹⁶⁶Ho has been separated from the bulk dysprosium target with the help of HPLC using Aminex A7 ion exchanger resin and -hydroxyisobutyric acid (-HIBA) as the mobile phase. The separation was quantitative and without any contamination from the dysprosium target. Method has also been developed to produce holmium free of -HIBA ligands. Attempts have been made to produce no-carrier-added recoiled ¹⁶⁶Ho and ¹⁶⁵Dy in water.     

Standardization of Fe by tracing method

This work describes the procedure followed by the Laboratório de Metrologia Nuclear (LMN) for the standardization of ⁵⁵Fe by the tracing method. This technique was applied using two radionuclides, which decay by the electron capture process followed by a prompt gamma-ray, namely ⁵¹Cr and ⁵⁴Mn, as tracers. The calibration was performed in a 4πβ–γ coincidence system. The efficiency was obtained by selecting a gamma-ray window set at the 320 keV total absorption peak for ⁵¹Cr and at 834 keV for ⁵⁴Mn.     

Determination of emission probabilities of gamma photons in the decay of Co

The emission probabilities of gamma photons in the decay of ⁵⁶Co were determined at Czech Metrology Institute (CMI) by means of an HPGe detector. This detector was calibrated experimentally and by MCNP-computation in the energy range from 40 to 2754 keV for a point source geometry and source-to-detector distance of 25 cm. Experimental and computed peak and total efficiencies were compared and calibration curves were determined. Full-peak efficiencies were calculated for all ⁵⁶Co γ-ray energies, and were used to calculate the emission probabilities. A set of point sources was prepared from a ⁵⁶Co solution. The solution was standardized using the 4πβ–γ coincidence method, and an ampoule was sent to international reference system for activity measurement of γ-ray emitting radionuclides (SIR). Each point source was measured with the HPGe detector at a source-to-detector distance of 25 cm. Coincidence emission probabilities of all the gamma photons were calculated and used to determine the summing correction factors.     

IBOX(2-(4′-dimethylaminophenyl)-6-iodobenzoxazole): a ligand for imaging amyloid plaques in the brain

It is well known that overproduction and accumulation of β-amyloid (Aβ) plaques in the brain is a key event in the pathogenesis of Alzheimer’s disease (AD). Previously it was demonstrated that [¹²⁵I]TZDM, 2-(4′-dimethylaminophenyl)-6-iodobenzothiazole, a thioflavin derivative, was an effective ligand with good in vitro and in vivo binding characteristics. To further improve the initial uptake and washout rate from the brain, important properties for in vivo imaging agents, a novel radioiodinated ligand, 2-(4′-dimethylaminophenyl)-6-iodobenzoxazole ([¹²⁵I]IBOX, 3), for detecting Aβ plaques in the brain, was synthesized and evaluated. The new iodinated ligand, IBOX, is based on an isosteric replacement of a sulfur atom of TZDM by an oxygen, by which the molecular weight is reduced while the lipophilicity of the iodinated ligand is increased. Partition coefficients (P.C.) of these two ligands were 70 and 124 for TZDM and IBOX, respectively. In vitro binding study indicated that the isosteric displacement yielded a new ligand with equal binding potency to Aβ(1–40) aggregates (K_i = 1.9 and 0.8 nM for TZDM and IBOX, respectively). Autoradiography of postmortem brain sections of a confirmed AD patient by [¹²⁵I]IBOX showed excellent labeling of plaques similar to that observed with [¹²⁵I]TZDM. More importantly, in vivo biodistribution of [¹²⁵I]IBOX in normal mice displayed superior peak brain uptake (2.08% at 30 min vs 1.57% at 60 min dose/brain for [¹²⁵I]IBOX and [¹²⁵I]TZDM, respectively). In addition, the washout from the brain was much faster for [¹²⁵I]IBOX as compared to [¹²⁵I]TZDM. Based on the data presented for [¹²⁵I]IBOX, it is predicted that the brain trapping of this new radioiodinated ligand in the Aβ containing regions will be more favorable than that of the parent compound, [¹²⁵I]TZDM. Further evaluation of [¹²⁵I]IBOX is warranted to confirm the Aβ plaque labeling properties in vivo.     

Measurement of depth distributions of H and C induced in concrete shielding of an electron accelerator facility

The estimation of radioactivity induced in concrete shielding is important for the decommissioning of accelerator facilities. Concentrations of ³H and ¹⁴C in the concrete shielding of an electron linear accelerator were measured, and the depth distributions of ³H, ¹⁴C and γ-ray emitters were discussed in relation to their formation reactions.     

Radiosynthesis of [F] N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane and the first human study with positron emission tomography

A procedure for the routine preparation of [¹⁸F]FP-CIT has been developed. Purification of the final product was achieved by preparative HPLC using phenethyl column without decomposition or epimerization. [¹⁸F] labeled-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane was prepared and PET imaging was performed on human subjects. A high uptake into striatal regions was observed. HPLC plasma analysis using [¹⁸F]FP-CIT indicated the presence of only one metabolite. By directly comparing the behavior of these three radiotracers ([¹⁸F]DOPA, [¹²³I]FP-CIT, and [¹⁸F]FP-CIT) in the same subjects, we can enhance our understanding of the dopaminergic system as well as the relative potential of these techniques in a clinical research setting.     

Standardization of (18)F using the 4pi(beta+gamma) integral counting technique.

Α 4π(β+γ) integral counting technique using a 4πβ−4πγ detector configuration was adopted for the standardization of ¹⁸F. In this technique, the β-detector is composed of two thin plastic scintillators sandwiching the source, coupled with a slender photomultiplier tube. The β-detector part with the source was inserted into a large well-type NaI(Tl) scintillation detector for γ-ray detection, making a 4πβ−4πγ coincidence counting system. In this work, positron particles were detected with high efficiency in the β-channel and annihilation quanta were also detected with high efficiency in the 4πγ channel. The very small inefficiency of the 4π(β+γ) integral counter for the β-plus branch has been confirmed by EGS5 Monte Carlo simulation. The result using this technique agreed within the uncertainties with the result obtained by the conventional 4πβ−γ coincidence counting with the efficiency extrapolation technique using the same detector configuration and a conventional 4πβ−γ coincidence counter.     

Fluorine-18 and carbon-11 labeled amphetamine analogs—Synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey

No-carrier-added (NCA) (±)-p-[¹⁸F]fluoroamphetamine (2a) and (±)-6-[¹⁸F]fluoro-3,4-methylene-dioxyamphetamine (2b) were synthesized through a multistep synthesis by nucleophilic substitution of the appropriate precursors (p-nitrobenzaldehyde, 1a and 6-nitropiperonal 1b, respectively) with [¹⁸F]fluoride followed by condensation with nitroethane and reduction with LAH in 20–30% yield (EOB) in a synthesis time of 90–109 min from EOB. NCA (−)-[¹¹C]methamphetamine (4a) and (±)-3,4-methylenedioxy-N-[¹¹C]methamphetamine (4b) were synthesized by methylation of the appropriate desmethyl precursors 3a and 3b with [¹¹C]H₃I in 40–60% yield (EOB) in a synthesis time of 30 min from EOB. Animal studies in mouse and rat revealed that the relative tissue uptake of these radiotracers was kidneys > lungs > liver > spleen > brain > heart > blood. The uptakes of these radiotracers in mouse brain were high and similar at 5 min post-injection (approx. 5%/g) but radioactivity then declined rapidly (approx. 1%/g at 60 min post-injection). For compounds 2a and 2b, the activity in the femur did not increase with time indicating in vivo defluorination may not be the major route of metabolism. Monoamine uptake inhibitors (nomifensine, fluoxetine and nisoxetine) did not inhibit but enhance the uptake of (−)-[¹¹C]methamphetamine (4a) in the rat brain by greater than 50%. A PET study in a Rhesus monkey revealed that the uptakes of (−)-[¹¹C]methamphetamine in different brain regions were similar and the retention of the radioactivity in these regions remained constant throughout the study. Analysis of arterial plasma by HPLC showed that 50% of radioactivity remained as 4a at 60 min post-injection.     

A Monte Carlo brachytherapy study for dose distribution prediction in an inhomogeneous medium

The purpose of this study was to present a theoretical analysis of how the presence of bone in interstitial brachytherapy affects dose rate distributions. This study was carried out using a Monte Carlo simulation of the dose distribution in homogeneous medium for 3 commonly used brachytherapy seeds. The 3 seeds investigated in this study are iridium-192 (¹⁹²Ir) iodine-125 (¹²⁵I), and palladium-103 (¹⁰³Pd). The computer code was validated by comparing the specific dose rate (Λ), the radial dose function g(r), and anisotropy function F(r,θ) for all 3 seeds with the AAPM TG-43 dosimetry formalism and current literature. The ¹⁹²Ir seed resulted in a dose rate of 1.115 ± 0.001 cGy-hr⁻¹-U⁻¹, the ¹²⁵I seed resulted in a dose rate of 0.965 ± 0.006 cGy/h⁻¹/U⁻¹, and the ¹⁰³Pd seed resulted in a dose rate of 0.671 ± 0.002 cGy/h⁻¹/U⁻¹. The results for all 3 seeds are in good agreement with the AAPM TG-43 and current literature. The validated computer code was then applied to a simple inhomogeneous model to determine the effect bone has on dose distribution from an interstitial implant. The inhomogeneous model showed a decrease in dose rate of 2% for the ¹⁹²Ir, an increase in dose rate of 84% for ¹²⁵I, and an increase in dose rate of 83% for the ¹⁰³Pd at the surface of the bone nearest to the source.     

Determination of 4.438 MeV γ-ray to neutron emission ratio from a Am–Be neutron source

Gamma-ray (γ-ray) spectra of a 1.49×10¹¹ Bq ²⁴¹Am–⁹Be source and background were measured using a 2 in×2 in, NaI(Tl) detector. Backgrounds due to the neutron interactions and energy deposition were calculated with MCNP4C. By subtracting the backgrounds from the experimental spectra, the S_γ is obtained and the R=S_γ/S_n was estimated. The final result of R=S_γ/S_n=0.596 is in agreement with result reported in literature.     

Synthesis of fatty acids specifically labelled with C in various positions, including H substitution, for in vivo studies of myocardium using PET

Fatty acids were labelled with ¹¹C in several positions by reacting [¹¹C]carbon dioxide with the appropriate Grignard reagent or by reacting a ,ω-bis-(bromo magnesium) alkane with a ¹¹C-labelled alkyl iodide followed by a reaction with carbon dioxide. The methyl and methylene ¹¹C-labelled fatty acids were obtained in 12–36% (decay corrected) radiochemical yield within 45–65 min, and with radiochemical purities higher than 96%. Perdeuterated ,ω-dibromo hexane, decane and tetradecane were synthesized from dimethylacetylene dicarboxylate by means of a Raney-nickel reduction in D₂O, Kolbe electrolysis and LAD reduction. The use of multiple isotopic labelling by the combination of position specific ¹¹C labelling and ²H substitution, has the potential to highlight different aspects of a complex biochemical system by PET. This principle is illustrated by results of the kinetics of different types of ¹¹C label of dodecanoic acid and the corresponding moieties of acetate. The combination of tracers allows the kinetics of β-oxidation of middle length carbon chain fatty acids and citric acid cycle metabolism to be separately assured, whilst deuteration of the tracers opens the possibility of highlighting the kinetics of the proton extraction processes reflecting rate limiting steps.