Development of a novel Indium-111 radiolabeled mogamulizumab targeting CCR4 for imaging adult T-cell leukemia/lymphoma in vivo
© 2021. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine..
OBJECTIVE: Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell lymphotropic virus type I (HTLV-1) infection, is among the most aggressive categories and has the worst prognosis among T-cell lymphomas. Mogamulizumab, an anti-CC chemokine receptor 4 (CCR 4), has been shown to be effective in the treatment of ATL; however, some ATL cases are often resistant, particularly the lymphoma-type ATL. To evaluate drug delivery in vivo and identify the distribution of CCR4-positive cells in the body, we developed a novel mogamulizumab tracer labeled with Indium-111 (111In) via diethylenetriaminepentaacetic acid (DTPA) for single-photon emission computerized tomography (SPECT), named [111In]In-DTPA-mogamulizumab, and evaluated its potential for visualizing CCR4 expression in vivo.
METHODS: [111In]In-DTPA-mogamulizumab was added to HCT116/CCR4 or HCT116/empty vector (EV) cells, and their radioactivity was measured 1 h after administration. A blocking study was additionally performed by treating HCT116/CCR4 cells with excess mogamulizumab in addition to [111In]In-DTPA-mogamulizumab. The biodistribution and SPECT imaging of [111In]In-DTPA-mogamulizumab in HCT116/CCR4 and HCT116/EV dual-xenografted BALB/c-nu mice were evaluated for 72 h after intravenous injection.
RESULTS: [111In]In-DTPA-mogamulizumab was acquired with a radiochemical purity > 95%. The cellular uptake level of [111In]In-DTPA-mogamulizumab by HCT116/CCR4 cells was significantly higher than that by HCT116/EV cells (HCT116/CCR4: 0.951 ± 0.069, HCT116/EV: 0.006 ± 0.001%dose/mg protein, p < 0.01), and the uptake was significantly suppressed by co-incubation with excess mogamulizumab (0.013 ± 0.003%dose/mg protein, p < 0.01). In the in vivo study, the radioactivity of the HCT116/CCR4 tumor tissue was significantly higher than that of the HCT116/EV tumor tissue at 72 h after the administration of [111In]In-DTPA-mogamulizumab (HCT116/CCR4: 20.5 ± 5.4, HCT116/EV: 5.7 ± 1.0%ID/g), and HCT116/CCR4 tumors were clearly and specifically visualized on SPECT imaging.
CONCLUSIONS: We have successfully developed a novel SPECT imaging tracer targeting CCR4, [111In]In-DTPA-mogamulizumab, which showed good specificity and pharmacokinetics, indicating potential in visualizing CCR4 expression in vivo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Annals of nuclear medicine - 36(2022), 3 vom: 15. März, Seite 319-326 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shimizu, Yoichi [VerfasserIn] |
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| Links: |
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| Themen: |
Adult T-cell leukemia |
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| Anmerkungen: |
Date Completed 04.04.2022 Date Revised 05.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12149-021-01706-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM335690572 |
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| 100 | 1 | |a Shimizu, Yoichi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Development of a novel Indium-111 radiolabeled mogamulizumab targeting CCR4 for imaging adult T-cell leukemia/lymphoma in vivo |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 04.04.2022 | ||
| 500 | |a Date Revised 05.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine. | ||
| 520 | |a OBJECTIVE: Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell lymphotropic virus type I (HTLV-1) infection, is among the most aggressive categories and has the worst prognosis among T-cell lymphomas. Mogamulizumab, an anti-CC chemokine receptor 4 (CCR 4), has been shown to be effective in the treatment of ATL; however, some ATL cases are often resistant, particularly the lymphoma-type ATL. To evaluate drug delivery in vivo and identify the distribution of CCR4-positive cells in the body, we developed a novel mogamulizumab tracer labeled with Indium-111 (111In) via diethylenetriaminepentaacetic acid (DTPA) for single-photon emission computerized tomography (SPECT), named [111In]In-DTPA-mogamulizumab, and evaluated its potential for visualizing CCR4 expression in vivo | ||
| 520 | |a METHODS: [111In]In-DTPA-mogamulizumab was added to HCT116/CCR4 or HCT116/empty vector (EV) cells, and their radioactivity was measured 1 h after administration. A blocking study was additionally performed by treating HCT116/CCR4 cells with excess mogamulizumab in addition to [111In]In-DTPA-mogamulizumab. The biodistribution and SPECT imaging of [111In]In-DTPA-mogamulizumab in HCT116/CCR4 and HCT116/EV dual-xenografted BALB/c-nu mice were evaluated for 72 h after intravenous injection | ||
| 520 | |a RESULTS: [111In]In-DTPA-mogamulizumab was acquired with a radiochemical purity > 95%. The cellular uptake level of [111In]In-DTPA-mogamulizumab by HCT116/CCR4 cells was significantly higher than that by HCT116/EV cells (HCT116/CCR4: 0.951 ± 0.069, HCT116/EV: 0.006 ± 0.001%dose/mg protein, p < 0.01), and the uptake was significantly suppressed by co-incubation with excess mogamulizumab (0.013 ± 0.003%dose/mg protein, p < 0.01). In the in vivo study, the radioactivity of the HCT116/CCR4 tumor tissue was significantly higher than that of the HCT116/EV tumor tissue at 72 h after the administration of [111In]In-DTPA-mogamulizumab (HCT116/CCR4: 20.5 ± 5.4, HCT116/EV: 5.7 ± 1.0%ID/g), and HCT116/CCR4 tumors were clearly and specifically visualized on SPECT imaging | ||
| 520 | |a CONCLUSIONS: We have successfully developed a novel SPECT imaging tracer targeting CCR4, [111In]In-DTPA-mogamulizumab, which showed good specificity and pharmacokinetics, indicating potential in visualizing CCR4 expression in vivo | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adult T-cell leukemia | |
| 650 | 4 | |a CCR4 | |
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| 650 | 4 | |a Mogamulizumab | |
| 650 | 4 | |a SPECT | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a CCR4 protein, human |2 NLM | |
| 650 | 7 | |a Indium Radioisotopes |2 NLM | |
| 650 | 7 | |a Receptors, CCR4 |2 NLM | |
| 650 | 7 | |a Indium-111 |2 NLM | |
| 650 | 7 | |a E9NGC49E0T |2 NLM | |
| 650 | 7 | |a mogamulizumab |2 NLM | |
| 650 | 7 | |a YI437801BE |2 NLM | |
| 700 | 1 | |a Koyasu, Sho |e verfasserin |4 aut | |
| 700 | 1 | |a Suzukida, Mari |e verfasserin |4 aut | |
| 700 | 1 | |a Izumi, Kiyotaka |e verfasserin |4 aut | |
| 700 | 1 | |a Kidera, Eitaro |e verfasserin |4 aut | |
| 700 | 1 | |a Shindo, Takero |e verfasserin |4 aut | |
| 700 | 1 | |a Saga, Tsuneo |e verfasserin |4 aut | |
| 700 | 1 | |a Ono, Masahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Takaori-Kondo, Akifumi |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamoto, Yuji |e verfasserin |4 aut | |
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