An emerging direction in nuclear medicine is the coupling of a therapeutic isotope with an imaging isotope to form a so-called theranostic pair, which allows one to quantitatively track and image the delivery of the therapeutic isotope. $^{90}\mathrm{Y}$ is used in several therapy applications and a convenient candidate imaging partner is the positron emitter $^{86}\mathrm{Y}$. A 27.6 MBq source of $^{86}\mathrm{Y}$ was produced at the University of Wisconsin and assayed with the Gammasphere array at Argonne National Laboratory. Over 200 $\ensuremath{\gamma}$-ray transitions were identified, more than double that which was previously known. The positron emission probability inferred from the present level scheme leads to 27.9(12)%, an important $(\ensuremath{\approx}14%)$ reduction with respect to the previously recommended value.
Abstract Experiments were performed to evaluate production of 72Se, parent radionuclide of the positron emitter 72As, at high energy at the Brookhaven Linac Isotope Producer (BLIP). Excitation functions for 75As(p, xn)72/75Se in the 52-105 MeV energy range were measured by irradiating thin gallium arsenide (GaAs) wafers. Maximum cross section value for the natAs(p, 4n)72Se reaction in the energy range was 103±9 mb at 52±1 MeV. Production size GaAs and arsenic metal (As°) targets were irradiated with 136 μA and 165 μA beam current possessing an initial Linac energy of 117 MeV. A total of 3.77±0.1 GBq (102±3 mCi) of 72Se was produced from a GaAs target at a calculated target entrance energy of 105.4 MeV, and 13.8±0.3 GBq (373±8 mCi) of 72Se from an As° target at a calculated incident energy of 49.5 MeV irradiated for 116.5 h and 68.9 h, respectively.
•New hexaazamacrobicyclic cage ligands•Cu(II); Co(II) complexation at μM concentrations•Ligands for further applications at physiological pH and rt
A diaminodihydroxyaryl derivative of ethylenediaminetetraacetic acid (DAHA-EDTA) was synthesised in two steps and evaluated for Cu-64 radiolabelling of the B72.3 antibody. The ligand complexes Cu-64 rapidly in a pH range 4 to 7. The Cu-64 complex of the parent species N,N′-bis(carboxymethyl)-N,N′-bis(2-hydroxyacetanilido)-1,2-diaminoethane (DHA-EDTA) shows good stability in serum at 37°C for up to 72 h. Conjugation of the Cu-64-DAHA-EDTA to the B72.3 antibody was achieved using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the activating agent. The reaction conditions were optimized for protein concentration and molar ratio of Cu-64-DAHA-EDTA and EDC to antibody. The specific activity of the final [Cu-64-DAHA-EDTA]-B72.3 product was 49 MBq mg−1 at the end of synthesis. The biodistribution of [Cu-64-DAHA-EDTA]-B72.3 in LS174t tumour-bearing nude mice was monitored over a 24 h period. Maximum tumour uptake (25.8 ± 7.5 % ID g−1) was achieved at 16 h and maintained at 24 h (21.6 ± 1.8 % ID g−1). Rapid clearance of the [Cu-64-DAHA-EDTA]-B72.3 from the blood resulted in good tumour-to-blood ratios (≈ 3.3) within a shorter period (6 h) than previously reported with B72.3 whole antibody and the LS174t tumour bearing nude mouse model.
The accelerator production of platinum isotopes was investigated at the Brookhaven Linac Isotope Producer BLIP). In this study high purity natural platinum foils were irradiated at 53.2, 65.7, 105.2, 151.9, 162.9 and 173.3. MeV. The irradiated foils were digested in aqua regia and then converted to their hydrochloride salt with concentrated hydrochloric acid before analyzing by gamma spectrometry periodically for at least 10 days post end of bombardment. A wide range of platinum (Pt), gold (Au) and iridium (Ir) isotopes were identified. Effective cross sections at BLIP for Pt-188, Pt-189, Pt-191 and Pt-195m were compared to literature and theoretical cross sections determined using Empire-3.2. The majority of the effective cross sections (<70 MeV) confirm those reported in the literature. While the absolute values of the theoretical cross sections were up to a factor of 3 lower, Empire 3.2 modeled thresholds and maxima correlated well with experimental values. Preliminary evaluation into a rapid separation of Pt isotopes from high levels of Ir and Au isotopes proved to be a promising approach for large scale production. In conclusion, this study demonstrated that with the use of isotopically enriched target material accelerator production of selected platinum isotopes is feasible over a wide proton energy range.
Rb-82 is a positron-emitting isotope used in cardiac positron emission tomography (PET) imaging which has been reported to deliver a significantly lower effective radiation dose than analogous imaging isotopes like Tl-201 and Tc-99m sestamibi. High-quality beta-decay data are essential to accurately appraise the total dose received by the patients. A source of Sr-82 was produced at the Brookhaven Linac Isotope Producer (BLIP), transported to Argonne National Laboratory, and studied with the Gammasphere facility. Significant revisions have been made to the level scheme of Kr-82 including 12 new levels, 50 new gamma-ray transitions, and the determination of many new spin assignments through angular correlations. These new high-quality data allow a precise reappraisal of the beta-decay strength function and thus the consequent dose received by patients.
Uracil derivatives, especially synthesised for use in positron emission tomography studies, are heated to form a gas phase source and introduced into a vacuum system by seeding into a helium jet. Through time of flight mass spectroscopy, these uracil compounds are shown to have resisted any thermal dissociation during the heating phase of introduction into the jet. The successful introduction into a beam clearly demonstrates that dissociative electron attachment, or other scattering or spectroscopic studies, could be performed on these compounds with confidence that the parent molecule remains intact, at least at the temperatures considered in this study. (C) 2016 Elsevier B.V. All rights reserved.
New hexaazamacrobicyclic cage bi-functional chelators (BFCs), 1-N-(3-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (m-SarAr) and 1-N-(2-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (o-SarAr), were synthesised. Their complexation with selected transitions metal ions i.e. CuII, CoII, and CdII was investigated over a range of pH at micromolar concentrations. CuII was complexed by m-SarAr and o-SarAr rapidly within 5 min in pH range of 5–9 at ambient temperature. In contrast, the complexation of CoII and CdII by these ligands was slower. The conjugation efficiencies of p-SarAr, m-SarAr, and o-SarAr to bovine serum albumin (BSA) were compared under various reactions. Conditions were optimised to a molar ratio of BSA/N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC)/BFC of 1 : 250 : 50 in pH 5 buffer for 30 min at ambient temperature. Under these conditions, the average number of p-SarAr, m-SarAr, or o-SarAr attached to BSA were determined to be 2.21 ± 0.16, 4.90 × 10–1 ± 2.48 × 10–2, and 2.67 × 10–2 ± 2.67 × 10–3, respectively. This fundamental study clearly demonstrates that the position of the amine on the phenyl ring has a significant effect on the metal complexation and conjugation reactions with BSA.
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
The cyclotron-based production of positron-emitting 61 Cu using the (p,α) reaction at 11.7 MeV was investigated starting from natural-zinc ( nat Zn) and enriched 64 Zn-foil targets, as well as its subsequent purification. For nat Zn, a combination of three resins were assessed to separate 61 Cu from contaminating 66,67,68 Ga and nat Zn. The specific activity of the purified 61 Cu determined using ICP-MS analysis ranged from 143.3 ± 14.3(SD) to 506.2 ± 50.6 MBq/µg while the titration method using p-SCN-Bn-DOTA, p-SCN-Bn-NOTA and diamsar gave variable results (4.7 ± 0.2–412.5 ± 15.3 MBq/µg), with diamsar lying closest to the ICP-MS values. Results suggest that the p-SCN-Bn-DOTA and p-SCN-Bn-NOTA titration methods are significantly affected by the presence of trace-metal contaminants.
The development of biomolecules as imaging probes requires radiolabeling methods that do not significantly influence their biodistribution. Sarcophagine (Sar) chelators form extremely stable complexes with copper and are therefore a promising option for labeling proteins with (64)Cu. However, initial studies using the first-generation sarcophagine bifunctional chelator SarAr to label the engineered antibody fragment ch14.18-ΔCH2 (MW 120 kDa) with (64)Cu showed high tracer retention in the kidneys, presumably because the high local positive charge on the Cu(II)-SarAr moiety resulted in increased binding of the labeled protein to the negatively charged basal cells of the glomerulus. To test this hypothesis, ch14.18-ΔCH2 was conjugated with a series of Sar derivatives of decreasing positive charge and three commonly used macrocyclic polyaza polycarboxylate (PAC) bifunctional chelators (BFC). The immunoconjugates were labeled with (64)Cu and injected into mice, and PET/CT images were obtained at 24 and 48 h postinjection (p.i.). At 48 h p.i., ex vivo biodistribution was assessed. In addition, to demonstrate the potential of metastasis detection using (64)Cu-labeled ch14.18-ΔCH2, a preclinical imaging study of intrahepatic neuroblastoma tumors was performed. Reducing the positive charge on the Sar chelators decreased kidney uptake of Cu-labeled ch14.18-ΔCH2 by more than 6-fold, from >45 to <6% ID/g, whereas the uptake in most other tissues, including liver, was relatively unchanged. However, despite this dramatic decrease, the renal uptake of the PAC BFCs was generally lower than that of the Sar derivatives, as was the liver uptake. Uptake of (64)Cu-labeled ch14.18-ΔCH2 in neuroblastoma hepatic metastases was detected using PET.
Model chromate-containing epoxy primer (CEP) films were applied to aluminium alloy substrates using doctor blades. The effect of exposure to NaCl solution on the chromate-containing epoxy film was followed by monitoring the leaching behaviour of Cr. The continuous leaching of chromate inhibitor from the epoxy film is a self-healing characteristic that is designed to prevent corrosion of the aluminium alloy substrate. The CEP films were doped with Cr-51 chromate inhibitor (t(1/2) = 27.7 days), were exposed to NaCl solutions over time, and the Cr-51 gamma emission was used to monitor its release from the film into the aqueous solution. Pulsed beam positron lifetime spectroscopy and scanning electron microscopy (SEM) were used to probe structural changes that might transport properties of chromate species in the epoxy matrix. Positron Annihilation Lifetime Spectroscopy (PALS) was used to determine changes to free volumes at the nano scale in the films and SEM was used to ascertain the chromate distribution and structural scales at the micron level and above. Both PALS and SEM studies were preformed as a function of exposure time. It was found that a SrCrO4 depletion zone was formed at the surface as a result of the complete dissolution of the inhibitor particles, suggesting that transport of the Sr2+ and CrO42- might be through a network of channels created by the voids remaining in the epoxy matrix. Published by Elsevier B.V.