<sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer Imaging
<b>Background:</b> The <sup>89</sup>Zr radioisotope is increasingly vital in positron emission tomography (PET), especially immuno-PET, due to its long half-life of 78.4 h, allowing extended tracking of biological processes. This makes it particularly suitable for researching...
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| author | Maria-Roxana Tudoroiu-Cornoiu Radu Marian Șerban Diana Cocioabă Dragoș Andrei Niculae Doina Drăgănescu Radu Leonte Alina Catrinel Ion Dana Niculae |
| author_facet | Maria-Roxana Tudoroiu-Cornoiu Radu Marian Șerban Diana Cocioabă Dragoș Andrei Niculae Doina Drăgănescu Radu Leonte Alina Catrinel Ion Dana Niculae |
| author_sort | Maria-Roxana Tudoroiu-Cornoiu |
| collection | DOAJ |
| description | <b>Background:</b> The <sup>89</sup>Zr radioisotope is increasingly vital in positron emission tomography (PET), especially immuno-PET, due to its long half-life of 78.4 h, allowing extended tracking of biological processes. This makes it particularly suitable for researching medicines with slow pharmacokinetics and enhances the precision of molecular imaging, especially in oncology. Despite zirconium’s potential for skeletal accumulation, effective chelation with agents like deferoxamine (DFO) enables high-resolution imaging of antigen-specific tumours, such as HER2-positive breast cancer, offering insights into tumour biology and treatment response. <b>Methods</b>: <sup>89</sup>Zr was produced at the ACSI TR-19 cyclotron via <sup>89</sup>Y(p,n)<sup>89</sup>Zr reaction. Natural yttrium foils (250 μm) were irradiated with 12.9 MeV protons on target, with 100 μA·h. An HER2-targeting affibody was synthesized and conjugated with p-NCS-Bz-DFO (1:4 mass ratio) at 37 °C for 60 min (pH 9.2 ± 0.2), then purified on a PD-10 column. Radiolabelling was performed with [<sup>89</sup>Zr]Zr-oxalate at pH ranging from 7.0 to 9.0, with concentrations from 110 to 460 MBq/mL. <b>Results</b>: Final activity reached 2.95 ± 0.31 GBq/batch (EOB corrected), with ≥ 99.9% radionuclide and ≥95% radiochemical purities. The anti-HER2 affibody was successfully radiolabelled with <sup>89</sup>Zr, resulting in a radiochemical purity of over 85% with molar activity of 26.5 ± 4.4 and 11.45 MBq/nmol at pH 7.0–7.5. In vitro tests on BT-474 and MCF-7 cell lines confirmed high uptake in HER2-positive cells, validating specificity and stability. <b>Conclusions</b>: The successful synthesis and labelling of the [<sup>89</sup>Zr]Zr-p-NCS-Bz-DFO-anti-HER2 affibody are promising achievements for its further application in targeted immuno-PET imaging for HER2-positive malignancies. Further in vivo studies are needed to support its clinical translation. |
| format | Article |
| id | doaj-art-c2259d9af9d94eacbd2911d6caa8a95b |
| institution | Matheson Library |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-c2259d9af9d94eacbd2911d6caa8a95b2025-06-25T14:18:13ZengMDPI AGPharmaceutics1999-49232025-06-0117673910.3390/pharmaceutics17060739<sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer ImagingMaria-Roxana Tudoroiu-Cornoiu0Radu Marian Șerban1Diana Cocioabă2Dragoș Andrei Niculae3Doina Drăgănescu4Radu Leonte5Alina Catrinel Ion6Dana Niculae7Radiopharmaceutical Research Centre (CCR), Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Măgurele, RomaniaRadiopharmaceutical Research Centre (CCR), Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Măgurele, RomaniaRadiopharmaceutical Research Centre (CCR), Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Măgurele, RomaniaRadiopharmaceutical Research Centre (CCR), Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Măgurele, RomaniaFaculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, RomaniaRadiopharmaceutical Research Centre (CCR), Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Măgurele, RomaniaFaculty of Chemical Engineering and Biotechnologies, Doctoral School of Applied Chemistry and Materials Science, National University of Science and Technology Politehnica Bucharest, 1-7 Gheorghe Polizu Street, 011061 Bucharest, RomaniaRadiopharmaceutical Research Centre (CCR), Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Măgurele, Romania<b>Background:</b> The <sup>89</sup>Zr radioisotope is increasingly vital in positron emission tomography (PET), especially immuno-PET, due to its long half-life of 78.4 h, allowing extended tracking of biological processes. This makes it particularly suitable for researching medicines with slow pharmacokinetics and enhances the precision of molecular imaging, especially in oncology. Despite zirconium’s potential for skeletal accumulation, effective chelation with agents like deferoxamine (DFO) enables high-resolution imaging of antigen-specific tumours, such as HER2-positive breast cancer, offering insights into tumour biology and treatment response. <b>Methods</b>: <sup>89</sup>Zr was produced at the ACSI TR-19 cyclotron via <sup>89</sup>Y(p,n)<sup>89</sup>Zr reaction. Natural yttrium foils (250 μm) were irradiated with 12.9 MeV protons on target, with 100 μA·h. An HER2-targeting affibody was synthesized and conjugated with p-NCS-Bz-DFO (1:4 mass ratio) at 37 °C for 60 min (pH 9.2 ± 0.2), then purified on a PD-10 column. Radiolabelling was performed with [<sup>89</sup>Zr]Zr-oxalate at pH ranging from 7.0 to 9.0, with concentrations from 110 to 460 MBq/mL. <b>Results</b>: Final activity reached 2.95 ± 0.31 GBq/batch (EOB corrected), with ≥ 99.9% radionuclide and ≥95% radiochemical purities. The anti-HER2 affibody was successfully radiolabelled with <sup>89</sup>Zr, resulting in a radiochemical purity of over 85% with molar activity of 26.5 ± 4.4 and 11.45 MBq/nmol at pH 7.0–7.5. In vitro tests on BT-474 and MCF-7 cell lines confirmed high uptake in HER2-positive cells, validating specificity and stability. <b>Conclusions</b>: The successful synthesis and labelling of the [<sup>89</sup>Zr]Zr-p-NCS-Bz-DFO-anti-HER2 affibody are promising achievements for its further application in targeted immuno-PET imaging for HER2-positive malignancies. Further in vivo studies are needed to support its clinical translation.https://www.mdpi.com/1999-4923/17/6/739zirconium-89pharmacokineticsradiopharmaceuticalsHER2-positiveaffibodybreast cancer |
| spellingShingle | Maria-Roxana Tudoroiu-Cornoiu Radu Marian Șerban Diana Cocioabă Dragoș Andrei Niculae Doina Drăgănescu Radu Leonte Alina Catrinel Ion Dana Niculae <sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer Imaging Pharmaceutics zirconium-89 pharmacokinetics radiopharmaceuticals HER2-positive affibody breast cancer |
| title | <sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer Imaging |
| title_full | <sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer Imaging |
| title_fullStr | <sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer Imaging |
| title_full_unstemmed | <sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer Imaging |
| title_short | <sup>89</sup>Zr-Radiolabelling of p-NCS-Bz-DFO-Anti-HER2 Affibody Immunoconjugate: Characterization and Assessment of In Vitro Potential in HER2-Positive Breast Cancer Imaging |
| title_sort | sup 89 sup zr radiolabelling of p ncs bz dfo anti her2 affibody immunoconjugate characterization and assessment of in vitro potential in her2 positive breast cancer imaging |
| topic | zirconium-89 pharmacokinetics radiopharmaceuticals HER2-positive affibody breast cancer |
| url | https://www.mdpi.com/1999-4923/17/6/739 |
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