First In Vivo and Phantom Imaging of Cyclotron-Produced 133La as a Theranostic Radionuclide for 225Ac and 135La.

Theranostic isotope pairs have gained recent clinical interest because they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to investigate cyclotron production of clinically relevant 133La activities using natural and isotopically enriched barium target material, compare fundamental PET phantom imaging characteristics of 133La with those of common PET radionuclides, and demonstrate in vivo preclinical PET tumor imaging using 133La-PSMA-I&T. Methods:133La was produced on a 24-MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched 135BaCO3, natBaCO3, and natBa metal. A synthesis unit performed barium/lanthanum separation. DOTA, PSMA-I&T, and macropa were radiolabeled with 133La. Derenzo and National Electrical Manufacturers Association phantom imaging was performed with 133La, 132La, and 89Zr and compared with 18F, 68Ga, 44Sc, and 64Cu. In vivo preclinical imaging was performed with 133La-PSMA-I&T on LNCaP tumor-bearing mice. Results: Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq of 133La and 28 ± 1 MBq of 135La using 135BaCO3, 59 ± 2 MBq of 133La and 35 ± 1 MBq of 135La using natBaCO3, and 81 ± 3 MBq of 133La and 48 ± 1 MBq of 135La using natBa metal. At 11.9 MeV, 135La yields were 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for 135BaCO3, natBaCO3, and natBa metal. BaCO3 target material recovery was 95.4% ± 1.7%. National Electrical Manufacturers Association and Derenzo phantom imaging demonstrated that 133La PET spatial resolution and scanner recovery coefficients were superior to those of 68Ga and 132La and comparable to those of 89Zr. The apparent molar activity was 130 ± 15 GBq/µmol with DOTA, 73 ± 18 GBq/µmol with PSMA-I&T, and 206 ± 31 GBq/µmol with macropa. Preclinical PET imaging with 133La-PSMA-I&T provided high-resolution tumor visualization with an SUV of 0.97 ± 0.17 at 60 min. Conclusion: With high-yield 133La cyclotron production, recovery of BaCO3 target material, and fundamental imaging characteristics superior to those of 68Ga and 132La, 133La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/α-therapy theranostic pair with 225Ac or as a PET/Auger electron therapy theranostic pair with 135La.

Taking cyclotron 68Ga production to the next level: Expeditious solid target production of 68Ga for preparation of radiotracers.

INTRODUCTION: Gallium-68 is an important radionuclide for positron emission tomography (PET) with steadily increasing applications of 68Ga-based radiopharmaceuticals for clinical use. Current 68Ga sources are primarily 68Ge/68Ga-generators, along with successful attempts of 68Ga production using a cyclotron. This study evaluated cyclotron 68Ga production and automated separation using expeditiously manufactured solid targets, demonstrates an order of magnitude improvement in yield compared to 68Ge/68Ga generators, and presents a convenient alternative to existing cyclotron production processes. A comparison of radiolabeling and preclinical PET imaging was performed with both cyclotron and generator produced 68Ga. METHODS: 100 mg enriched 68Zn (99.3% 68Zn, 0.48% 67Zn, 0.1% 66Zn) pellets pressed on silver discs were bombarded for 20-75 min using 12.5 MeV proton beam energies and 10-30 µA currents. 68Ga was separated using an automated TRASIS AllinOne synthesizer employing AG 50W-X8 and UTEVA resins. Post-separation recovery of the 68Zn by electrolysis yielded 76.7 ± 4.3%. Radionuclidic purity of cyclotron-produced 68Ga was investigated with gamma spectroscopy using a HPGe-detector. Radiolabeling was investigated using the macrocyclic chelator DOTA and the bombesin-derived peptide NOTA-BBN2. PET imaging was performed using [68Ga]Ga-NOTA-BBN2 in a PC3 xenograft model. RESULTS: 600 µA·min fresh and recycled quadruplet 68Zn target irradiations (n = 8) at 12.5 MeV and 30 µA yielded 13.9 ± 1.0 GBq 68Ga; 2200 µA·min irradiations (n = 3) yielded 37.5 ± 1.9 GBq 68Ga. HPGe analysis showed EOB 0.0074% and 0.0084% of total activity of 66Ga and 67Ga, respectively. Metal impurities were 0.06 ± 0.03 µg/GBq Zn, 0.13 ± 0.007 µg/GBq Fe, and 0.02 ± 0.01 µg/GBq Al for cyclotron 68Ga. Cyclotron and 68Ge/68Ga generator 68Ga respective DOTA and NOTA-BBN2 labeling incorporations were 99.4 ± 0.0% and 99.3 ± 0.2%, and 90.4 ± 1.5% and 93.0 ± 3.6% determined by radio-thin layer chromatography (radio-TLC). Preclinical PET imaging comparison between generator and cyclotron produced 68Ga showed identical radiotracer tumor uptake and biodistribution profiles in PC3 tumor bearing mice. CONCLUSIONS: Cyclotron 68Ga production provides highly scalable production with equivalent or superior quality 68Ga to a 68Ge/68Ga generator, while providing identical biodistribution and tumor uptake profiles. Our described targetry is simpler and more cost-effective than existing liquid and solid targetry, enabling a turnkey production system for multi-facility distribution of cyclotron produced 68Ga. The manufacturing simplicity described has potential applications for producing other radiometals such as 44Sc. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Our cost-effective method of solid target 68Ga production can enhance 68Ga production capabilities to meet the high demand for 68Ga-radiopharmaceuticals for research and clinical use.

Dust is the dominant source of "heavy metals" to peat moss (Sphagnum fuscum) in the bogs of the Athabasca Bituminous Sands region of northern Alberta.

Sphagnum fuscum was collected from twenty-five ombrotrophic (rain-fed) peat bogs surrounding open pit mines and upgrading facilities of Athabasca Bituminous Sands (ABS) in northern Alberta (AB) in order to assess the extent of atmospheric contamination by trace elements. As a control, this moss species was also collected at a bog near Utikuma (UTK) in an undeveloped part of AB and 264km SW of the ABS region. For comparison, this moss was also collected in central AB, in the vicinity of the City of Edmonton which is approximately 500km to the south of the ABS region, from the Wagner Wetland which is 22km W of the City, from Seba Beach (ca. 90km W) and from Elk Island National Park (ca. 45km E). All of the moss samples were digested and trace elements concentrations determined using ICP-SMS at a commercial laboratory, with selected samples also analyzed using instrumental neutron activation analysis at the University of Alberta. The mosses from the ABS region yielded lower concentrations of Ag, As, Bi, Cd, Cu, Pb, Sb, Tl, and Zn compared to the moss from the Edmonton area. Concentrations of Ni and Mo in the mosses were comparable in these two regions, but V was more abundant in the ABS samples. Compared with the surface vegetation of eight peat cores collected in recent years from British Columbia, Ontario, Quebec and New Brunswick, the mean concentrations of Ag, As, Bi, Cd, Cu, Mo, Ni, Pb, Sb, Tl and Zn in the mosses from the ABS region are generally much lower. In fact, the concentrations of these trace elements in the samples from the ABS region are comparable to the corresponding values in forest moss from remote regions of central and northern Norway. Lithophile element concentrations (Ba, Be, Ga, Ge, Li, Sc, Th, Ti, Zr) explain most of the variation in trace metal concentrations in the moss samples. The mean concentrations of Th and Zr are greatest in the moss samples from the ABS region, reflecting dust inputs to the bogs from open pit mines, aggregate quarries, and gravel roads. Linear regressions of V, Ni, and Mo (elements enriched in bitumen) versus Sc (a conservative, lithophile element) show excellent correlations in the mosses from the ABS region, but this is true also of Ag, Pb, Sb and Tl: thus, most of the variation in the trace metal concentrations can be explained simply by the abundance of dust particles on the plants of this region. Unlike the moss samples from the ABS region and from UTK where Pb/Sc ratios resemble those of crustal rocks, the moss samples from the other regions studied yielded much greater Pb/Sc ratios implying significant anthropogenic Pb contributions at these other sites.

Overview of the Full-scale Radiological Dispersal Device Field Trials.

In 2012, Defence Research and Development Canada, in partnership with a number of other Canadian and International organizations, led a series of three field trials designed to simulate a Radiological Dispersal Device (RDD). These trials, known as the Full-Scale RDD (FSRDD) Field Trials, involved the explosive dispersal of a short-lived radioactive tracer ((140)La, t1/2 = 40.293 h). The FSRDD Field Trials required a significant effort in their planning, preparation, and execution to ensure that they were carried out in a safe, efficient manner and that the scientific goals of the trials were met. The discussion presented here details the planning and execution of the trials, outlines the relevant radiation safety aspects, provides a summary of the source term and atmospheric conditions for the three dispersal events, and provides an overview of the measurements that were made to track the plumes and deposition patterns.