Production of 89Zr via the 89Y(p,n)89Zr reaction in aqueous solution: Effect of solution composition on in-target chemistry

Pandey, Mukesh K.; Engelbrecht, Hendrik; Byrne, John F.; Packard, Alan B.; DeGrado, Timothy R.

doi:10.1016/j.nucmedbio.2014.01.006

Cited by 59 publications

(101 citation statements)

References 34 publications

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“…395.5 keV) [3] and its half-life of 78.4 h is an optimal match for the pharmacokinetics of most mAbs. [4] The aqueous chemistry of zirconium is dominated by the 4+ oxidation state.…”

Section: Introductionmentioning

confidence: 99%

Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of ⁸⁹Zirconium for Positron Emission Tomography (PET) Imaging

et al. 2016

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Four novel chelators (L1–L4) and their 89zirconium complexes were prepared and compared with the 89zirconium desferrioxamine B (DFO) complex. The new chelates are based on 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) scaffolds and present either three or four hydroxamate arms for coordination with Zr4+ ions with coordination numbers between six and eight. The 89Zr–L4 complex showed similar stability to that of 89Zr–DFO when incubated in either rat blood plasma or ethylenediaminetetraacetic acid challenge experiments. Positron imaging and biodistribution studies in mice showed that 89Zr–L4 had similar pharmacokinetic behavior to that of 89Zr–DFO, with rapid renal elimination and low residual activity in background tissues. A bifunctional version of L4 (L5) was synthesized and conjugated to trastuzumab; an anti-HER2/neu antibody. Immunopositron emission tomography imaging and biodistribution with 89Zr–L5–trastuzumab revealed high tumor to background ratios (tumor/blood ratio: 14.2 ± 2.25) and a high tumor specificity that was comparable to the performance of 89Zr–DFO–trastuzumab.

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“…395.5 keV) [3] and its half-life of 78.4 h is an optimal match for the pharmacokinetics of most mAbs. [4] The aqueous chemistry of zirconium is dominated by the 4+ oxidation state.…”

Section: Introductionmentioning

confidence: 99%

Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of ⁸⁹Zirconium for Positron Emission Tomography (PET) Imaging

et al. 2016

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“…Targets have been prepared using foils, pressed powders, and sputtered material . The production of this radionuclide via the irradiation of dissolved yttrium salts has also been investigated . Irradiations with protons <14 MeV are typically used to prevent the coproduction of 88 Zr, an undesirable long‐lived impurity.…”

Section: Radiometals For Theranostic Applicationsmentioning

confidence: 99%

Radiometals for imaging and theranostics, current production, and future perspectives

Mikołajczak

Meulen

Lapi

2019

Labelled Comp Radiopharmac

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The aim of this review is to make the reader familiar with currently available radiometals, their production modes, capacities, and quality concerns related to their medical use, as well as new emerging radiometals and irradiation technologies from the perspective of their diagnostic and theranostic applications. Production methods of 177Lu serve as an example of various issues related to the production yield, specific activity, radionuclidic and chemical purity, and production economy. Other radiometals that are currently used or explored for potential medical applications, with particular focus on their theranostic value, are discussed. Using radiometals for diagnostic imaging and therapy is on the rise. The high demand for radiometals for medical use prompts investigations towards using alternative irradiation reactions, while using existing nuclear reactors and accelerator facilities. This review discusses these production capacities and what is necessary to cover the growing demand for theranostic nuclides.

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“…Incident proton energy was degraded from 16.4 2 O and 12 mL of concentrated nitric acid were added to sufficient water to bring the total volume to 1.8 mL. The concentration of HNO 3 (;0.1N) was sufficient to prevent in-target precipitation of copper hydroxide while reducing water radiolysis (13). The Cu(NO 3 ) 2 Á xH 2 O solution (1.8 mL) was loaded into the cyclotron target using an automated valve system (13,14).…”

Section: Production and Purification Of 63 Znmentioning

confidence: 99%

“…The concentration of HNO 3 (;0.1N) was sufficient to prevent in-target precipitation of copper hydroxide while reducing water radiolysis (13). The Cu(NO 3 ) 2 Á xH 2 O solution (1.8 mL) was loaded into the cyclotron target using an automated valve system (13,14). The target was pressurized with air (40-45 psi) and irradiated at 20 mA for 60 min.…”

Section: Production and Purification Of 63 Znmentioning

confidence: 99%

Preparation and Preliminary Evaluation of ⁶³Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc

et al. 2014

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Abnormalities of zinc homeostasis are indicated in many human diseases. A noninvasive imaging method for monitoring zinc in the body would be useful to understand zinc dynamics in health and disease. To provide a PET imaging agent for zinc, we have investigated production of 63 Zn (half-life, 38.5 min) via the 63 Cu(p,n) 63 Zn reaction using isotopically enriched solutions of 63 Cu-copper nitrate. A solution target was used for rapid isolation of the 63 Zn radioisotope from the parent 63 Cu ions. Initial biologic evaluation was performed by biodistribution and PET imaging in normal mice. Methods: To produce 63 Zn, solutions of 63 Cu-copper nitrate in dilute nitric acid were irradiated by 14-MeV protons in a low-energy cyclotron. An automated module was used to purify 63 Zn from 63 Cu in the target solution. The 63 Cu-63 Zn mixture was trapped on a cation-exchange resin and rinsed with water, and the 63 Zn was eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized with NaHCO 3 , and the 63 Zn was then trapped on a carboxymethyl cartridge, washed with water, and eluted with isotonic 4% sodium citrate. Standard quality control tests were performed on the product according to current good manufacturing practice, including radionuclidic identity and purity, and measurement of nonradioactive Zn 12 , Cu 12 , Fe 13 , and Ni 12 by ion-chromatography high-performance liquid chromatography. Biodistribution and PET imaging studies were performed in B6.SJL mice after intravenous administration of 63 Zn-zinc citrate. 63 Cu target material was recycled by eluting the initial resin with 4N HNO 3 . Results: Yields of 1.07 ± 0.22 GBq (uncorrected at 30-36 min after end of bombardment) of 63 Zn-zinc citrate were obtained with a 1.23 M 63 Cu-copper nitrate solution. Radionuclidic purity was greater than 99.9%, with copper content lower than 3 μg/batch. Specific activities were 41.2 ± 18.1 MBq/μg (uncorrected) for the 63 Zn product. PET and biodistribution studies in mice at 60 min showed expected high uptake in the pancreas (standard uptake value, 8.8 ± 3.2), liver (6.0 ± 1.9), upper intestine (4.7 ± 2.1), and kidney (4.2 ± 1.3). Conclusion: A practical and current good manufacturing practice-compliant preparation of radionuclidically pure 63 Zn-zinc citrate has been developed that will enable PET imaging studies in animal and human studies. 63 Zn-zinc citrate showed the expected biodistribution in mice.

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Production of 89Zr via the 89Y(p,n)89Zr reaction in aqueous solution: Effect of solution composition on in-target chemistry

Cited by 59 publications

References 34 publications

Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of ⁸⁹Zirconium for Positron Emission Tomography (PET) Imaging

Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of ⁸⁹Zirconium for Positron Emission Tomography (PET) Imaging

Radiometals for imaging and theranostics, current production, and future perspectives

Preparation and Preliminary Evaluation of ⁶³Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc

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Production of 89Zr via the 89Y(p,n)89Zr reaction in aqueous solution: Effect of solution composition on in-target chemistry

Cited by 59 publications

References 34 publications

Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of 89Zirconium for Positron Emission Tomography (PET) Imaging

Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of 89Zirconium for Positron Emission Tomography (PET) Imaging

Radiometals for imaging and theranostics, current production, and future perspectives

Preparation and Preliminary Evaluation of 63Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc

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Product

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Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of ⁸⁹Zirconium for Positron Emission Tomography (PET) Imaging

Macrocycle‐Based Hydroxamate Ligands for Complexation and Immunoconjugation of ⁸⁹Zirconium for Positron Emission Tomography (PET) Imaging

Preparation and Preliminary Evaluation of ⁶³Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc