scholarly journals Microfluidic Preparation of 89Zr-Radiolabelled Proteins by Flow Photochemistry

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 764
Author(s):  
Daniel F. Earley ◽  
Amaury Guillou ◽  
Dion van der Born ◽  
Alex J. Poot ◽  
Jason P. Holland
Keyword(s):  
Positron Emission Tomography ◽  
Human Serum Albumin ◽  
Radiochemical Purity ◽  
Flow Reactor ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Flow Process ◽  
Automated Production ◽  
Desferrioxamine B ◽  
Positron Emission

89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2 ± 1.3% (n = 3) and radiochemical purity >90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6 ± 3.6% (n = 3) with an equivalent RCP > 90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus and optimisation of the method are required before the flow process is competitive with manual reactions.

scholarly journals Microfluidic Preparation of 89Zr-Radiolabelled Proteins by Flow Photochemistry

2021 ◽  
Author(s):  
Daniel F. Earley ◽  
Amaury Guillou ◽  
Dion van der Born ◽  
Alex J. Poot ◽  
Jason P. Holland
Keyword(s):  
Positron Emission Tomography ◽  
Human Serum Albumin ◽  
Radiochemical Purity ◽  
Flow Reactor ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Flow Process ◽  
Automated Production ◽  
Desferrioxamine B ◽  
Positron Emission

89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2±1.3% (n = 3) and radiochemical purity >90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6±3.6% (n = 3) with an equivalent RCP >90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus, and optimisation of the method is required before the flow process is competitive with manual reactions.

scholarly journals Automated Light-Induced Synthesis of 89Zr-Radiolabeled Antibodies for Immuno-Positron Emission Tomography

2021 ◽  
Author(s):  
Simon Klingler ◽  
Jason Holland
Keyword(s):  
Positron Emission Tomography ◽  
Nuclear Medicine ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Desferrioxamine B ◽  
Automated Method ◽  
Isolation And Characterization ◽  
Positron Emission ◽  
The Many ◽  
Radiolabeled Antibodies

Abstract Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography (PET) imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in <25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our Good Laboratory Practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in <25 min with an overall decay-corrected radiochemical yield of 20.1±2.4% (n=3), a radiochemical purity >99%, and chemical purity >99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

scholarly journals Automated light-induced synthesis of 89Zr-radiolabeled antibodies for immuno-positron emission tomography

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Simon Klingler ◽  
Jason P. Holland
Keyword(s):  
Positron Emission Tomography ◽  
Nuclear Medicine ◽  
Positron Emission Tomography Imaging ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Desferrioxamine B ◽  
Automated Method ◽  
Isolation And Characterization ◽  
Positron Emission ◽  
Radiolabeled Antibodies

AbstractClinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

18F-Endothelin-1, a positron emission tomography (PET) radioligand for the endothelin receptor system: radiosynthesis and in vivo imaging using microPET

2002 ◽  
Vol 103 (s2002) ◽  
pp. 4S-8S ◽  
Author(s):  
Peter JOHNSTRÖM ◽  
Neil G. HARRIS ◽  
Tim D. FRYER ◽  
Olivier BARRET ◽  
John C. CLARK ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Receptor System ◽  
Endothelin 1 ◽  
Positron Emission ◽  
Pharmacokinetic Properties ◽  
Rats And Mice ◽  
Lung And Kidney

Positron emission tomography (PET) is a powerful technique with the sensitivity to image and quantify receptor-bound radioligands in vivo. Recent progress in PET scanner technology has resulted in the development of dedicated tomographs designed for small animals, with resolution that allows the delineation of discrete organs and their larger substructures in rats and mice. Our aim was to determine whether endothelin-1 (ET-1) could be labelled with 18F, and whether the resulting 18F-ET-1 would have the required pharmacokinetic properties to permit binding and imaging of ET receptors in vivo. 18F-ET-1 could be produced in a total radiochemical yield of 5.9±0.7% in 207±3min (n = 20). Specific radioactivities were in the range 220–370GBq/µmol, and the radiochemical purity of the isolated 18F-ET-1 was >95%. In vivo distribution in the rat was studied using microPET. High levels of 18F-ET-1 uptake were found in lung and kidney, whereas liver showed moderate levels of uptake. The resolution of the microPET scanner was sufficient to differentiate heterogeneous uptake in subrenal structures in the rat.

scholarly journals Clinical Value of Positron Emission Tomography(PET) Using Automated Production System of Oxygen-15 Water.

RADIOISOTOPES ◽  
1996 ◽  
Vol 45 (11) ◽  
pp. 689-695
Author(s):  
Yoshiharu YONEKURA ◽  
Yoshio ISHIDA ◽  
Yasuhiro MAGATA ◽  
Yoshinori MIYAKE ◽  
Kohei HAYASHIDA ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Production System ◽  
Emission Tomography ◽  
Clinical Value ◽  
Automated Production ◽  
Positron Emission ◽  
Oxygen 15 Water

A desferrioxamine B squaramide ester for the incorporation of zirconium-89 into antibodies

2016 ◽  
Vol 52 (80) ◽  
pp. 11889-11892 ◽  
Author(s):  
Stacey E. Rudd ◽  
Peter Roselt ◽  
Carleen Cullinane ◽  
Rodney J. Hicks ◽  
Paul S. Donnelly
Keyword(s):  
Breast Cancer ◽  
Positron Emission Tomography ◽  
Mouse Models ◽  
Positron Emission Tomography Imaging ◽  
Emission Tomography ◽  
Tomography Imaging ◽  
Ester Derivative ◽  
Desferrioxamine B ◽  
Positron Emission

A squaramide ester derivative of desferrioxamine B is used to attach zirconium-89 to the antibody trastuzumab and the new conjugate is used for positron emission tomography imaging in mouse models of breast cancer.

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