We report a single-molecule radiotracer that can be labeled independently with F-18-fluoride or radiometals (Cu-64, Lu-177) in a single step. A prostate-specific membrane antigen (PSMA)-targeting ligand, armed with both an organotrifluoroborate and a metal-chelator (DOTA), was designed to optionally afford F-18-, Cu-64- or Lu-177-labeled products that were injected into mice bearing prostate cancer (LNCaP) xenografts. PET/CT images and ex vivo biodistribution data show high, specific tumor uptake irrespective of which radionuclide is used, thereby demonstrating a new approach to combining, in a single molecule, F-18-labeling capabilities for PET imaging with radiometalation for potential imaging and therapeutic applications.

A scalable recycling technique for the recovery of Mo-100 from previously irradiated and chemically processed targets is described. A combined process for both Cu and Ta supported targets and the respective ` waste' solutions has been developed. This process involves selectively dissolving Cu target backings from undissolved portions of Mo-100 pellets; precipitating Cu(OH)(2) at pH 9; electrochemical removal of Cu traces; precipitating (NH4)(2)MoO4 at pH 2.5-3; thermally decomposing (NH4)(2)MoO4; and H-2 reduction of MoO3 to Mo metal. Radionuclidic decontamination by a factor of similar to 100 is observed, while overall Mo-100 recovery from initial target plating to recycled Mo metal of 96% is achieved.

Micromatter Technologies Inc., now located in Surrey B.C., Canada, is a worldwide supplier of pure and boron containing diamond-like carbon (DLC) stripper foils ranging from 10 nm to 10 mu m-house using pulsed laser deposition. Continuing our research into novel production methods and alternative materials to be used as beam strippers for heavy elements and in particular for tandem particle accelerators, pure boron foils were prepared by laser plasma ablation of a disc shaped boron sputter target. Foil thickness between 10 mu m to approximately 0.7 mu m were achieved. The new boron foils showed considerably less stress, higher mechanical strength and better flexibility than comparable DLC films.

A scalable recycling technique for the recovery of 100Mo from previously irradiated and chemically processed targets is described. A combined process for both Cu and Ta supported targets and the respective ‘waste’ solutions has been developed. This process involves selectively dissolving Cu target backings from undissolved portions of 100Mo pellets; precipitating Cu(OH)2 at pH 9; electrochemical removal of Cu traces; precipitating (NH4)2MoO4 at pH 2.5-3; thermally decomposing (NH4)2MoO4; and H2 reduction of MoO3 to Mo metal. Radionuclidic decontamination by a factor of ~100 is observed, while overall 100Mo recovery from initial target plating to recycled Mo metal of 96% is achieved.

Mercury (Hg) is one of the most hazardous environmental pollutants. It exists in a large number of physical and chemical forms; individual properties of the element and its compounds determine its complex environmental distribution, biological enrichment and eventually its toxicity. The most frequently encountered chemical forms are elemental mercury (Hg), inorganic mercury (mainly Hg), monomethylmercury (MMHg, CH3Hg ) and dimethylmercury (DMHg, CH3HgCH3). The toxic effects of mercury depend on various properties of the respective mercury compound, such as its solubility, valence state and lipophilicity.

The chiral acyclic "pa" ligand (pa = picolinic acid) H2CHXdedpa (N4O2) and two NI-containing dedpa analogues (H2CHXdedpa-N,N'-propyl-2-NI, H2dedpa-N,N'-propyl-2-NI, NI = nitroimidazole) were studied as chelators for copper radiopharmaceuticals (CHX = cyclohexyl, H2dedpa = 1,2-[[carboxypyridin-2-yl]methylamino]ethane). The hexadentate ligand H2CHXdedpa was previously established as a superb system for (67/68)Ga radiochemistry. The solid state X-ray crystal structures of [Cu(CHXdedpa-N,N'-propyl-2-NI)] and [Cu(dedpa-N,N'-propyl-2-NI)] reveal the predicted hexadentate, distorted octahedral binding of the copper(ii) ion. Cyclic voltammetry of [Cu(dedpa-N,N'-propyl-2-NI)] shows that there is one reversible couple associated with the NI redox, and one irreversible but reproducible couple attributed to the Cu(ii)/Cu(i) redox cycle. Quantitative radiolabeling (>99%) of CHXdedpa(2-) and (dedpa-N,N'-propyl-2-NI)(2-) with (64)Cu was achieved under fast and efficient labeling conditions (10 min, RT, 0.5 M sodium acetate buffer, pH 5.5) at ligand concentrations as low as 10(-6) M. In vitro kinetic inertness studies of the (64)Cu labelled complexes were studied in human serum at 37 °C over 24 hours; [(64)Cu(CHXdedpa)] was found to be 98% stable compared to previously investigated [(64)Cu(dedpa)] which was only 72% intact after 24 hours.

Published online: October 20, 2014. 2014;55:1910-1914. J Nucl Med. Thomas J. Ruth and Paul Schaffer François Bénard, Stefan K. Zeisler, Milan Vuckovic, Kuo-Shyan Lin, Zhengxing Zhang, Nadine Colpo, Xinchi Hou, Low-Specific-Activity Molybdenum Tc-Pertechnetate from 99m Cross-Linked Polyethylene Glycol Beads to Separate http://jnm.snmjournals.org/content/55/11/1910 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml Information about reproducing figures, tables, or other portions of this article can be found online at:

99mTc is currently produced by an aging fleet of nuclear reactors, which require enriched uranium and generate nuclear waste. We report the development of a comprehensive solution to produce 99mTc in sufficient quantities to supply a large urban area using a single medical cyclotron. Methods: A new target system was designed for 99mTc production. Target plates made of tantalum were coated with a layer of 100Mo by electrophoretic deposition followed by high-temperature sintering. The targets were irradiated with 18-MeV protons for up to 6 h, using a medical cyclotron. The targets were automatically retrieved and dissolved in 30% H2O2. 99mTc was purified by solid-phase extraction or biphasic exchange chromatography. Results: Between 1.04 and 1.5 g of 100Mo were deposited on the tantalum plates. After high-temperature sintering, the 100Mo formed a hard, adherent layer that bonded well with the backing surface. The targets were irradiated for 1–6.9 h at 20–240 μA of proton beam current, producing up to 348 GBq (9.4 Ci) of 99mTc. The resulting pertechnetate passed all standard quality control procedures and could be used to reconstitute typical anionic, cationic, and neutral technetium radiopharmaceutical kits. Conclusion: The direct production of 99mTc via proton bombardment of 100Mo can be practically achieved in high yields using conventional medical cyclotrons. With some modifications of existing cyclotron infrastructure, this approach can be used to implement a decentralized medical isotope production model. This method eliminates the need for enriched uranium and the radioactive waste associated with the processing of uranium targets.

We report a kit-based approach for the purification of sodium pertechnetate (99mTcO4−) from solutions with high MoO42− content. Methods: Cross-linked polyethylene glycol resins (ChemMatrix) were used to separate 99mTc and molybdenum in 4N NaOH. The resins were loaded at various flow rates and eluted with water to release 99mTc. The 99mTc solution was passed through a cation exchange resin and an alumina cartridge, followed by saline elution. This process was tested with cyclotron-produced 99mTc using an automated system and disposable kits. Results: Optimal results were obtained by loading 500 mg of resin at flow rates of up to 3.1 mL/min, with quantitative extraction of 99mTc from the molybdate solution and complete release of 99mTc after elution with water. The automated system was highly efficient at isolating Na99mTcO4 within minutes, with a recovery rate of 92.7% ± 1.1% (mean ± SD) using cyclotron-produced 99mTc. Conclusion: ChemMatrix resins were highly effective at separating 99mTcO4− from molybdate solutions.

The Applied Technology Group at TRIUMF operates three accelerators, TR30-1, TR30-2 and CP42 that use 30 MeV proton beams in the generation of commercial radioisotopes. These cyclotrons typically use diamond-like carbon (DLC) stripper foils produced in house of between 2.0 and 3.0 μm to extract particle beams from these cyclotrons. Micromatter (formerly the TRIUMF Carbon Foil Laboratory) manufactures DLC foils in a range of thicknesses from 10 nm to ~10 μm using pulsed laser deposition. Continuing our previous work ‘(Zeisler and Jaggi Nucl Instrum Methods Phys Res A 613:434, 2010)’ we further investigated the presence of boron in multilayer DLC foils, specifically DLC/boron/DLC hybrid foils. In this work, we investigated the mechanical properties and lifetime of these stripper foils in cyclotrons with varying thicknesses and boron content as well as a special DLC layer deposited by chemical vapor deposition and find an improvement in flexibility, mechanical strength and lifetime.

This paper details the electrodeposition of metallic molybdenum from an aqueous electrolyte containing molybdate ions. The deposition is performed in an acetate bath that contains a high (up to 10M) concentration of acetate. The molybdenum deposits are thick (up to 20μm), adherent and were characterized by XRD and XPS analysis. The deposition is inefficient, with most of the current (up to 99%) used in the electrolysis of water to generate hydrogen. The effect of acetate concentration, pH, additives and current on the deposition efficiency and physical properties of the molybdenum deposit were investigated and optimized to obtain smooth, adherent coatings.

TRIUMF operates several high power industrial cyclotrons for the commercial production of isotopes for radiological diagnostics and therapy. Two of these accelerators, TR30-1 and TR30-2, are capable of delivering H− beams of 30MeV and beam currents in excess of 1000μA. For many years, in-house produced diamond-like carbon (DLC) foils of various compositions have been utilized to extract proton beams from these cyclotrons (Zeisler and Jaggi, 2008) [1].

The TRIUMF Applied Technology Group operates several high-power industrial cyclotrons for commercial radioisotope production. Two of these accelerators, TR30-1 and TR30-2, can deliver H(-) beams of 30 MeV and beam currents in excess of 1000 mu A. For many years, in-house produced diamondlike carbon (DLC) foils of approximately 2.0-3.0 mu m thickness have been utilized to extract proton beams from these accelerators.The TRIUMF Carbon Foil Laboratory uses pulsed laser deposition to manufacture DLC films in a wide thickness range (10 nm to similar to 10 mu m). It is known that the quality and the composition of the graphite sputter target used in the laser ablation process has a significant effect on the mechanical properties of the deposited film as well as its durability in ion beams. Encouraged by the findings of Sugai et al. [1], we investigated the production of stripper foils by laser ablation of graphite/boron composites as well as multilayer foils using pure graphite and boron targets. (C) 2009 Elsevier B.V. All rights reserved.

Along with use for stripping and timing of high energy ions in accelerator experiments, ultra-thin DLC foils are being successfully applied to the instrumentation for fusion and space plasma research. In the latter case, the foils are exposed to light ions and neutral atoms in the keV energy range. Unlike high energy ion irradiations, the foil lifetime is determined by thinning of the foil due to sputtering by particles that transit the foil. In this work, sputtering of thin (1–3μg/cm2) DLC foils produced by two different techniques such as modified glow discharge deposition and laser plasma ablation has been investigated using high intensity He+ beams at 4keV. A loss of foil material under ion impact was estimated from on-line measurements of energy loss of transmitting ions by means of an electrostatic analyzer. For comparison, samples of arc-deposited carbon foils were also evaluated. To avoid any carbon build up on the foils under ion irradiation, the measurements were carried out in an oil-free vacuum environment. Calculated from the measurements, results on both threshold fluence and total sputtering yield of the foils for the incident He+ ions are presented together with some extrapolations to other low energy projectiles of fusion plasma interest. This enables an estimate for operational lifetime of the DLC foils determined by sputtering.

The TRIUMF Applied Technology Group operates high-power industrial cyclotrons for commercial radioisotope production. Two of these cyclotrons, TR30-1 and TR30-2, are capable of accelerating H- ions to an energy of 30MeV and beam currents in excess of 1000 mu A. For many years, amorphous carbon foils of approximately 2.0 mu m thickness have been utilized to extract proton beams from these accelerators.Novel multilayer foils consisting of layers of amorphous and diamond-like carbon (DLC) of 2.0 +/- 0.2 mu m thickness were manufactured in-house by carbon arc and pulsed laser deposition, respectively. In the TR30 cyclotrons, the new composite foils with 25% DLC content show a three times longer lifetime than the purely amorphous foils, while maintaining their excellent physical and mechanical characteristics during irradiation. (C) 2008 Elsevier B.V. All rights reserved.

PURPOSE:In vivo detection of apoptosis is a diagnostic tool with potential clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV) is an ideal probe for in vivo apoptosis detection owing to its strong affinity for phosphatidylserine (PS), the molecular flag on the surface of apoptotic cells. Most clinical studies performed to visualize apoptosis have used (99m)Tc-anxV; however, its poor distribution profile often compromises image quality. In this study, tumor apoptosis after therapy was visualized by positron emission tomography (PET) using (64)Cu-labeled streptavidin (SAv), following pre-targeting of apoptotic cells with biotinylated anxV.METHODS:Apoptosis was induced in tumor-bearing mice by photodynamic therapy (PDT) using phthalocyanine dyes as photosensitizers, and red light. After PDT, mice were injected i.v. with biotinylated anxV, followed 2 h later by an avidin chase, and after another 2 h with (64)Cu-DOTA-biotin-SAv. PET images were subsequently recorded up to 13 h after PDT.RESULTS:PET images delineated apoptosis in treated tumors as early as 30 min after (64)Cu-DOTA-biotin-SAv administration, with tumor-to-background ratios reaching a maximum at 3 h post-injection, i.e., 7 h post-PDT. Omitting the administration of biotinylated anxV or the avidin chase failed to provide a clear PET image, confirming that all three steps are essential for adequate visualization of apoptosis. Furthermore, differences in action mechanisms between photosensitizers that target tumor cells directly or via initial vascular stasis were clearly recognized through differences in tracer uptake patterns detecting early or delayed apoptosis.CONCLUSION:This study demonstrates the efficacy of a three-step (64)Cu pretargeting procedure for PET imaging of apoptosis. Our data also confirm the usefulness of small animal PET to evaluate cancer treatment protocols.