A semi-automated system for the routine production of copper-64

Kume, Maiko; Carey, Paul D.; Gaehle, Gregory; Madrid, Evelyn; Voller, Thomas; Margenau, W.; Welch, Michael J.; Lapi, Suzanne E.

doi:10.1016/j.apradiso.2012.03.009

Cited by 55 publications

(54 citation statements)

References 7 publications

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“…Although most PET radiometals are still at the research stage, automated separation modules are still useful for many of the same reasons, but principally to minimize dose to personnel. Several groups have published on custom-made automated modules for various radiometals, including 64 Cu [41][42][43][44] 89 Zr [48,49]. In this work, we have designed, built and commissioned a module that has performed the chemical separation of 89 Zr safely and routinely, at activities in excess of 50 mCi, with high radionuclidic purity and satisfactory ESA.…”

Section: +mentioning

confidence: 99%

Routine Production of 89Zr Using an Automated Module

et al. 2013

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89Zr has emerged as a useful radioisotope for targeted molecular imaging via positron emission tomography (PET) in both animal models and humans. This isotope is particularly attractive for cancer research because its half-life (t 1/2 = 3.27 days) is well-suited for in vivo targeting of macromolecules and nanoparticles to cell surface antigens expressed by cancer cells. Furthermore, 89Zr emits a low-energy positron (E β+,mean = 0.40 MeV), which is favorable for high spatial resolution in PET, with an adequate branching ratio for positron emission (BR = 23%). The demand for 89 Zr for research purposes is increasing; however, 89Zr also emits significant gamma radiation (Γ 15 keV = 6.6 Rcm 2 /mCih), which makes producing large amounts of this isotope by hand unrealistic from a radiation safety standpoint. Fortunately, a straightforward method exists for production of Zr safely and routinely, at activities in excess of 50 mCi, with radionuclidic purity > 99.9% and satisfactory effective specific activity (ESA).

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Section: +mentioning

confidence: 99%

Routine Production of 89Zr Using an Automated Module

et al. 2013

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“…64 Cu was prepared as previously described (12). Radioactivity was counted with a Beckman g-8000 counter containing a NaI crystal (Beckman Instruments, Inc.).…”

Section: Generalmentioning

confidence: 99%

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

et al. 2016

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The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent 64 Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location. Methods: New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0-to 60-min dynamic whole-body PET/MR examination was performed after injection of approximately 111 MBq of 64 Cu-ATSM. After 24 h, a 0-to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of 18 F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 α subunit ). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test. Results: Elevated uptake of 64 Cu-ATSM was found in the rabbits' IF compared with the SF. 64 Cu-ATSM imaging demonstrated IF-to-SF SUV mean ratios (±SD) of 1.75 ± 0.21 and 2.30 ± 0.26 at 4 and 8 wk after injury, respectively. 18 F-FDG imaging demonstrated IF-to-SF SUV mean ratios of 1.84 ± 0.12 at 8 wk after injury. IF-to-BM SUV mean ratios were significantly higher (P , 0.001) than SF-to-BM SUV mean ratios both 4 and 8 wk after injury for 64 Cu-ATSM and 8 wk after injury for 18 F-FDG (P , 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1α. Conclusion: The results show that hypoxia is present in this rabbit model of atherosclerosis and suggest that 64 Cu-ATSM PET/MR is a potentially promising method for the detection of hypoxic and potentially vulnerable atherosclerotic plaque in human subjects. At herosclerosis is a systemic degenerative and inflammatory vascular disease that develops over decades, leading to advanced lesions characterized by a lipid core separated from the lumen by a fibrous cap. It has been recognized that plaque composition more than the degree of luminal stenosis determines the risk of acute clinical events (e.g., stroke, myocardial infarction) (1). Macrophage-rich plaques with a thin fibrous cap, large lipid core, and abundance of leaky microvessels tend to be more vulnerable (1). The rupture or erosion of the fibrous cap in vulnerable plaque may lead to thromboembolization and arterial occlusion (2,3).According to the anoxemia theory of atherosclerosis, an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerotic lesions (4). In the initial s...

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“…To radiolabel the nanoparticles, high specific activity 64 Cu (14000±7600 Ci/mmol or 518±28 TBq/mmol) was obtained from the Washington University School of Medicine (St. Louis, MO, USA). 64 Cu was produced on a CS-15 biomedical cyclotron by the 64 Ni(p,n) 64 Cu nuclear reaction using previously established methods 29 , with a half-life of 12.7 hours. Following PEGylation (described above), particles were characterized as described above by TGA and reacted in 0.1 M Na 2 CO3 buffer (pH 9) with 2-(4-isothiocyanatobenzyl) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA) at 5 mg/mL (2:1 DOTA:AEM molar ratio).…”

Section: Methodsmentioning

confidence: 99%

Subtumoral analysis of PRINT nanoparticle distribution reveals targeting variation based on cellular and particle properties

Roode

Brighton

Tao

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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The biological activity of nanoparticle-directed therapies critically depends on cellular targeting. We examined the subtumoral fate of Particle Replication in Non-Wetting Templates (PRINT) nanoparticles in a xenografted melanoma tumor model by multi-color flow cytometry and in vivo confocal tumor imaging. These approaches were compared with the typical method of whole-organ quantification by radiolabeling. In contrast to radioactivity based detection which demonstrated a linear dose-dependent accumulation in the organ, flow cytometry revealed that particle association with cancer cells became dose-independent with increased particle doses and that the majority of the nanoparticles in the tumor were associated with cancer cells despite a low fractional association. In vivo imaging demonstrated an inverse relationship between tumor cell association and other immune cells, likely macrophages. Finally, variation in particle size nonuniformly affected subtumoral association. This study demonstrates the importance of subtumoral targeting when assessing nanoparticle activity within tumors.

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A semi-automated system for the routine production of copper-64

Cited by 55 publications

References 7 publications

Routine Production of 89Zr Using an Automated Module

Routine Production of 89Zr Using an Automated Module

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

Subtumoral analysis of PRINT nanoparticle distribution reveals targeting variation based on cellular and particle properties

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A semi-automated system for the routine production of copper-64

Cited by 55 publications

References 7 publications

Routine Production of 89Zr Using an Automated Module

Routine Production of 89Zr Using an Automated Module

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model

Subtumoral analysis of PRINT nanoparticle distribution reveals targeting variation based on cellular and particle properties

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PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model