Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT
No effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of <sup>111</sup>In-labeled anti-SFTSV antibodies targeting SFTSV...
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MDPI AG
2024-12-01
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| Online Access: | https://www.mdpi.com/1420-3049/30/1/38 |
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| author | Takeshi Fuchigami Mya Myat Ngwe Tun Yusuke Tanahara Kodai Nishi Sakura Yoshida Kazuma Ogawa Morio Nakayama Daisuke Hayasaka |
| author_facet | Takeshi Fuchigami Mya Myat Ngwe Tun Yusuke Tanahara Kodai Nishi Sakura Yoshida Kazuma Ogawa Morio Nakayama Daisuke Hayasaka |
| author_sort | Takeshi Fuchigami |
| collection | DOAJ |
| description | No effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of <sup>111</sup>In-labeled anti-SFTSV antibodies targeting SFTSV structural proteins as single-photon emission computed tomography (SPECT) imaging agents for the selective visualization of SFTSV-infected sites. This study used nuclear medicine imaging to elucidate the pathology of SFTS and assess its therapeutic efficacy. Immunostaining experiments confirmed that the anti-SFTSV antibody (N-mAb), which targets the N protein, specifically accumulated in SFTSV-infected Vero E6 cells. <sup>111</sup>In-labeled N-mAb was successfully prepared using a diethylenetriaminepentaacetic acid (DTPA) chelator, resulting in [<sup>111</sup>In]In-DTPA-N-mAb with high radiochemical purity exceeding 95% and a radiochemical yield of 55%. Cell-binding assays using SFTSV-infected Vero E6 cells demonstrated that [<sup>111</sup>In]In-DTPA-N-mAb binding was detectable even without membrane permeabilization, with the binding intensity correlating with infection levels. In vivo studies using SFTSV-infected A129 mice showed high spleen accumulation of [<sup>111</sup>In]In-DTPA-N-mAb (87.5% ID/g), consistent with SFTSV tropism, compared to 12.3% ID/g in mock-infected mice. SPECT/CT imaging clearly revealed high radioactivity in these regions. Although nonspecific accumulation was noted in the liver and spleen, this issue may be mitigated through antibody modifications such as fragmentation or PEGylation. Overall, [<sup>111</sup>In]In-DTPA-N-mAb is a promising imaging agent for non-invasive visualization of SFTSV-infected sites and may aid in elucidating SFTS pathology and assessing therapeutic efficacy. |
| format | Article |
| id | doaj-art-107616afdb9e41afb6ebc9d8c90dec30 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-107616afdb9e41afb6ebc9d8c90dec302025-01-10T13:18:41ZengMDPI AGMolecules1420-30492024-12-013013810.3390/molecules30010038Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECTTakeshi Fuchigami0Mya Myat Ngwe Tun1Yusuke Tanahara2Kodai Nishi3Sakura Yoshida4Kazuma Ogawa5Morio Nakayama6Daisuke Hayasaka7Laboratory of Clinical Analytical Sciences, Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, JapanCenter for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases, Shimane University, Izumo 690-8504, JapanDepartment of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, JapanDepartment of Radioisotope Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanDepartment of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, JapanLaboratory of Clinical Analytical Sciences, Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, JapanDepartment of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, JapanLaboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8511, JapanNo effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of <sup>111</sup>In-labeled anti-SFTSV antibodies targeting SFTSV structural proteins as single-photon emission computed tomography (SPECT) imaging agents for the selective visualization of SFTSV-infected sites. This study used nuclear medicine imaging to elucidate the pathology of SFTS and assess its therapeutic efficacy. Immunostaining experiments confirmed that the anti-SFTSV antibody (N-mAb), which targets the N protein, specifically accumulated in SFTSV-infected Vero E6 cells. <sup>111</sup>In-labeled N-mAb was successfully prepared using a diethylenetriaminepentaacetic acid (DTPA) chelator, resulting in [<sup>111</sup>In]In-DTPA-N-mAb with high radiochemical purity exceeding 95% and a radiochemical yield of 55%. Cell-binding assays using SFTSV-infected Vero E6 cells demonstrated that [<sup>111</sup>In]In-DTPA-N-mAb binding was detectable even without membrane permeabilization, with the binding intensity correlating with infection levels. In vivo studies using SFTSV-infected A129 mice showed high spleen accumulation of [<sup>111</sup>In]In-DTPA-N-mAb (87.5% ID/g), consistent with SFTSV tropism, compared to 12.3% ID/g in mock-infected mice. SPECT/CT imaging clearly revealed high radioactivity in these regions. Although nonspecific accumulation was noted in the liver and spleen, this issue may be mitigated through antibody modifications such as fragmentation or PEGylation. Overall, [<sup>111</sup>In]In-DTPA-N-mAb is a promising imaging agent for non-invasive visualization of SFTSV-infected sites and may aid in elucidating SFTS pathology and assessing therapeutic efficacy.https://www.mdpi.com/1420-3049/30/1/38severe fever thrombocytopenia syndromesingle-photon emission computed tomographyindium-111antibody |
| spellingShingle | Takeshi Fuchigami Mya Myat Ngwe Tun Yusuke Tanahara Kodai Nishi Sakura Yoshida Kazuma Ogawa Morio Nakayama Daisuke Hayasaka Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT Molecules severe fever thrombocytopenia syndrome single-photon emission computed tomography indium-111 antibody |
| title | Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT |
| title_full | Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT |
| title_fullStr | Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT |
| title_full_unstemmed | Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT |
| title_short | Development of <sup>111</sup>In-Labeled Monoclonal Antibodies Targeting SFTSV Structural Proteins for Molecular Imaging of SFTS Infectious Diseases by SPECT |
| title_sort | development of sup 111 sup in labeled monoclonal antibodies targeting sftsv structural proteins for molecular imaging of sfts infectious diseases by spect |
| topic | severe fever thrombocytopenia syndrome single-photon emission computed tomography indium-111 antibody |
| url | https://www.mdpi.com/1420-3049/30/1/38 |
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