Excitation function of 54Fe(p,α)51Mn from 9.5 MeV to 18 MeV.

Excitation function of the 54Fe(p,α)51Mn reaction was measured from 9.5 to 18 MeV E 0 , p + by activating a foil stack of 54Fe electrodeposited on copper substrates. Residual radionuclides were quantified by HPGe gamma ray spectrometry. Both 51Mn (t 1/2 = 46.2 min, 〈 E ß + 〉 = 963.7 keV , I ß + = 97 % ; E γ = 749.1 keV, I γ = 0.265%) and its radioactive daughter, 51Cr (t 1/2 = 27.704d, E γ = 320.1 keV, I γ = 9.91%), were used to indirectly quantify formation of 51Mn. Results agree within uncertainty to the only other measurement in literature and predictions of default TALYS theoretical code. Final relative uncertainties are within ±12%.

Production, Collection, and Purification of 47Ca for the Generation of 47Sc through Isotope Harvesting at the National Superconducting Cyclotron Laboratory.

An experiment was performed at the National Superconducting Cyclotron Laboratory using a 140 MeV/nucleon 48Ca beam and a flowing-water target to produce 47Ca for the first time with this production route. A production rate of 0.020 ± 0.004 47Ca nuclei per incoming beam particle was measured. An isotope harvesting system attached to the target was used to collect radioactive cationic products, including 47Ca, from the water on a cation-exchange resin. The 47Ca collected was purified using three separation methods optimized for this work: (1) DGA extraction chromatography resin with HNO3 and HCl, (2) AG MP-50 cation-exchange resin with an increasing concentration gradient of HCl, and (3) AG MP-50 cation-exchange resin with a methanolic HCl gradient. These methods resulted in ≥99 ± 2% separation yield of 47Ca with 100% radionuclidic purity within the limits of detection for HPGe measurements. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was used to identify low levels of stable ions in the water of the isotope harvesting system during the irradiation and in the final purified solution of 47Ca. For the first time, this experiment demonstrated the feasibility of the production, collection, and purification of 47Ca through isotope harvesting for the generation of 47Sc for nuclear medicine applications.

A 224Ra-labeled polyoxopalladate as a putative radiopharmaceutical.

Despite their attractive properties, internal targeted alpha therapies using 223/224Ra are limited to bone-seeking applications. As there is no suitable chelator available, the search for new carriers to stably bind Ra2+ and to connect it to biological target molecules is necessary. Polyoxopalladates represent a class of compounds where Ra2+ can be easily introduced into the Pd-POM core during a facile one-pot preparation. Due to the formation of a protein corona, the connection to other targeting (bio)macromolecules is possible.

Recent progress using the Staudinger ligation for radiolabeling applications.

The increasing application of positron emission tomography and single-photon emission computer tomography in radiopharmacy and nuclear medicine has stimulated the development of a multitude of novel and versatile bioorthogonal conjugation techniques. Currently, there is particular interest in radiolabeling biologically active, high molecular weight compounds like peptides, proteins, or antibodies, but also for the labeling of small organic compounds. An enormous challenge in radiolabeling these biologically active molecules is that the introduction of radiohalogens like fluorine-18 as well as various radiometals proceeds under harsh conditions, which could destroy the biomolecule. The Staudinger ligation is one of the most powerful bioorthogonal conjugation techniques. The reaction proceeds over wide temperature and pH ranges; an amide (peptide) bond is formed as the ligation unit, which minimizes distortion of the structure; no isomers are obtained; and the reaction proceeds without any metal catalyst. Due to this adaptability, this robust ligation type is a perfect candidate with a high potential for various applications in the field of radiopharmacy for the labeling of biomolecules under mild conditions. This review summarizes recent research concerning the implementation of the Staudinger ligation for radiolabeling applications.

Correction: Synthesis, dynamic NMR characterization and XRD studies of novel N,N'-substituted piperazines for bioorthogonal labeling.

[This corrects the article DOI: 10.3762/bjoc.12.242.].

Bulk production and evaluation of high specific activity 186gRe for cancer therapy using enriched 186WO3 targets in a proton beam.

INTRODUCTION: Rhenium-186g (t1/2 = 3.72 d) is a ß- emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction 185Re(n,γ)186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched 186W results in a 186gRe product with a higher specific activity, allowing it to be used more broadly for targeted radiotherapy applications. This targets the unmet clinical need for more efficient radiotherapeutics. METHODS: A target consisting of highly enriched, pressed 186WO3 was irradiated with protons at the Los Alamos National Laboratory Isotope Production Facility (LANL-IPF) to evaluate 186gRe product yield and quality. LANL-IPF was operated in a dedicated nominal 40 MeV mode. Alkaline dissolution followed by anion exchange chromatography was used to isolate 186gRe from the target material. Phantom and radiolabeling studies were conducted with the produced 186gRe activity. RESULTS: A 186gRe batch yield of 1.38 ± 0.09 MBq/µAh or 384.9 ± 27.3 MBq/C was obtained after 16.5 h in a 205 µA average/230µA maximum current proton beam. The chemical recovery yield was 93% and radiolabeling was achieved with efficiencies ranging from 60-80%. True specific activity of 186gRe at EOB was determined via ICP-AES and amounted to 0.788 ± 0.089 GBq/µg (0.146 ± 0.017 GBq/nmol), which is approximately seven times higher than the product obtained from neutron capture in a reactor. Phantom studies show similar imaging quality to the gold standard 99mTc. CONCLUSIONS: We report a preliminary study of the large-scale production and novel anion exchange based chemical recovery of high specific activity 186gRe from enriched 186WO3 targets in a high-intensity proton beam with exceptional chemical recovery and radiochemical purity.

Accelerator-based production of the (99m)Tc-(186)Re diagnostic-therapeutic pair using metal disulfide targets (MoS2, WS2, OsS2).

Novel, natural abundance metal disulfide targets were irradiated for 1h with a 10µA proton beam in a small, medical cyclotron. Osmium disulfide was synthesized by simple distillation and precipitation methods while MoS2 and WS2 were commercially available. The targets dissolved under mild conditions and were analyzed by γ-spectroscopy. Production rates and potential applications are discussed, including target recovery and recycling schemes for OsS2 and WS2.

Incorporation of gallium-68 into the crystal structure of Prussian blue to form K(68)GaxFe1-x[Fe(CN)6] nanoparticles: toward a novel bimodal PET/MRI imaging agent.

Similarity between the Ga(+) ion and the Fe(3+) ion allows for partial replacement of Fe(3+) ions with Ga(3+) ions in the Fe(iii) crystallographic positions in Prussian blue (PB) to form various solid solutions KGaxFe1-x[Fe(CN)6] (0 < x < 1). Such solid solutions possess very high thermodynamic stability as expected from the parent PB structure. Consequently, a simple one-step (68)Ga-labeling method was developed for preparing a single-phase nanoparticulate bimodal PET/MRI imaging agent based on the PB structural platform. Unlike the typical (68)Ga-labelling reaction based on metal complexation, this novel chelator-free (68)Ga-labeling reaction was shown to be kinetically fast under the acidic conditions. The Ga(3+) ion does not hydrolyze, and affords the (68)Ga-labelled PB nanoparticles, which are easy to purify and have extremely high stability against radionuclidic leaching in aqueous solution.

Chromatographic separation of germanium and arsenic for the production of high purity (77)As.

A simple column chromatographic method was developed to isolate (77)As (94±6% (EtOH/HCl); 74±11 (MeOH)) from germanium for potential use in radioimmunotherapy. The separation of arsenic from germanium was based on their relative affinities for different chromatographic materials in aqueous and organic environments. Using an organic or mixed mobile phase, germanium was selectively retained on a silica gel column as germanate, while arsenic was eluted from the column as arsenate. Subsequently, enriched (76)Ge (98±2) was recovered for reuse by elution with aqueous solution (neutral to basic). Greater than 98% radiolabeling yield of a (77)As-trithiol was observed from methanol separated [(77)As]arsenate [17].

Synthesis, dynamic NMR characterization and XRD studies of novel N,N'-substituted piperazines for bioorthogonal labeling.

Novel, functionalized piperazine derivatives were successfully synthesized and fully characterized by 1H/13C/19F NMR, MS, elemental analysis and lipophilicity. All piperazine compounds occur as conformers resulting from the partial amide double bond. Furthermore, a second conformational shape was observed for all nitro derivatives due to the limited change of the piperazine chair conformation. Therefore, two coalescence points were determined and their resulting activation energy barriers were calculated using 1H NMR. To support this result, single crystals of 1-(4-nitrobenzoyl)piperazine (3a, monoclinic, space group C2/c, a = 24.587(2), b = 7.0726(6), c = 14.171(1) Å, ß = 119.257(8)°, V = 2149.9(4) Å3, Z = 4, Dobs = 1.454 g/cm3) and the alkyne derivative 4-(but-3-yn-1-yl)-1-(4-fluorobenzoyl)piperazine (4b, monoclinic, space group P21/n, a = 10.5982(2), b = 8.4705(1), c = 14.8929(3) Å, ß = 97.430(1)°, V = 1325.74(4) Å3, Z = 4, Dobs = 1.304 g/cm3) were obtained from a saturated ethyl acetate solution. The rotational conformation of these compounds was also verified by XRD. As proof of concept for future labeling purposes, both nitropiperazines were reacted with [18F]F-. To test the applicability of these compounds as possible 18F-building blocks, two biomolecules were modified and chosen for conjugation either using the Huisgen-click reaction or the traceless Staudinger ligation.

Chromatographic separation of selenium and arsenic: A potential (72)Se/(72)As generator.

An anion exchange method was developed to separate selenium and arsenic for potential utility in a (72)Se/(72)As generator. The separation of the daughter (72)As from the (72)Se parent is based on the relative acid-base behavior of the two oxo-anions in their highest oxidation states. At pH 1.5, selenate is retained on strongly basic anion exchange resin as HSeO4(-) and SeO4(2-), while neutral arsenic acid, H3AsO4, is eluted.