First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin
Abstract Background Activation of endothelial cells and platelets in atherothrombosis is characterized by upregulation of P-selectin. As a consequence, P-selectin represents a potential target for molecular imaging to identify thrombosis at an early stage. Fucoidan is a polysaccharide ligand extract...
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2024-11-01
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| Online Access: | https://doi.org/10.1186/s13550-024-01173-8 |
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| author | Reindert F. Oostveen Kang H. Zheng Yannick Kaiser Nick S. Nurmohamed Jeffrey Kroon Tim C. de Wit Edwin Poel Joel Aerts Francois Rouzet Erik S. G. Stroes Didier Letourneur Hein J. Verberne Cédric Chauvierre Mia R. Ståhle |
| author_facet | Reindert F. Oostveen Kang H. Zheng Yannick Kaiser Nick S. Nurmohamed Jeffrey Kroon Tim C. de Wit Edwin Poel Joel Aerts Francois Rouzet Erik S. G. Stroes Didier Letourneur Hein J. Verberne Cédric Chauvierre Mia R. Ståhle |
| author_sort | Reindert F. Oostveen |
| collection | DOAJ |
| description | Abstract Background Activation of endothelial cells and platelets in atherothrombosis is characterized by upregulation of P-selectin. As a consequence, P-selectin represents a potential target for molecular imaging to identify thrombosis at an early stage. Fucoidan is a polysaccharide ligand extracted from brown algae with nanomolar affinity for P-selectin. This first-in-human study evaluated in healthy volunteers the safety, whole-body biodistribution, and dosimetry of 99mTc-fucoidan (Good Manufacturing Practices grade). We also investigated whether we could observe binding of 99mTc-fucoidan to human thrombi ex vivo and in vivo. In ten healthy volunteers, conjugate whole-body scans were performed up to 24 h following intravenous injection of 99mTc-fucoidan (370 MBq). Moreover, 99mTc-fucoidan uptake in ex vivo human thrombi (n = 11) was measured by gamma counting. Additionally, three patients with a newly diagnosed deep vein thrombosis (DVT) were subjected to 99mTc-fucoidan SPECT/CT imaging. Results 99mTc-fucoidan was well tolerated in all participants without any drug-related adverse events. The total-body absorbed dose in males was comparable to females (0.012 ± 0.004 vs. 0.011 ± 0.005 mSv/MBq; p = 0.97). Gamma counting experiments demonstrated binding of tracer to ex vivo human thrombi that was 16% lower after blocking with a natural P-selectin ligand, Sialyl Lewis X. 99mTc-fucoidan demonstrated specific uptake at the thrombus site in one out of three scanned patients with DVT. Conclusions 99mTc-Fucoidan has a favorable biodistribution and safety profile. 99mTc-fucoidan exhibited specific binding to human thrombi in both in vivo and ex vivo settings. Nonetheless, the in vivo results do not support further clinical investigation of 99mTc-fucoidan as an imaging modality for DVT. Other clinical implementations of a technetium− 99m-labeled P-selectin tracer should be considered. Trial registration: Clinicaltrials,NCT03422055.Registered 01/15/2018. URL: https://clinicaltrials.gov/study/NCT03422055 Landelijk Trial Register, NL7739. Registered 4/2/2019 . https://onderzoekmetmensen.nl/en/trial/26785 |
| format | Article |
| id | doaj-art-34a2387182cc4b73afcd6d215acffb5e |
| institution | Kabale University |
| issn | 2191-219X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | SpringerOpen |
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| series | EJNMMI Research |
| spelling | doaj-art-34a2387182cc4b73afcd6d215acffb5e2024-11-24T12:42:45ZengSpringerOpenEJNMMI Research2191-219X2024-11-011411910.1186/s13550-024-01173-8First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectinReindert F. Oostveen0Kang H. Zheng1Yannick Kaiser2Nick S. Nurmohamed3Jeffrey Kroon4Tim C. de Wit5Edwin Poel6Joel Aerts7Francois Rouzet8Erik S. G. Stroes9Didier Letourneur10Hein J. Verberne11Cédric Chauvierre12Mia R. Ståhle13Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamDepartment of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamDepartment of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamDepartment of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamDepartment of Experimental Vascular Medicine, Amsterdam UMC, University of AmsterdamDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of AmsterdamDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of AmsterdamNuclear Medicine Department, Bichat Hospital, APHPNuclear Medicine Department, Bichat Hospital, APHPDepartment of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamUMR-S U1148 INSERM, Laboratory for Vascular Translational Science (LVTS), Université Paris Cité, Université Sorbonne Paris NordDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, University of AmsterdamUMR-S U1148 INSERM, Laboratory for Vascular Translational Science (LVTS), Université Paris Cité, Université Sorbonne Paris NordDepartment of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamAbstract Background Activation of endothelial cells and platelets in atherothrombosis is characterized by upregulation of P-selectin. As a consequence, P-selectin represents a potential target for molecular imaging to identify thrombosis at an early stage. Fucoidan is a polysaccharide ligand extracted from brown algae with nanomolar affinity for P-selectin. This first-in-human study evaluated in healthy volunteers the safety, whole-body biodistribution, and dosimetry of 99mTc-fucoidan (Good Manufacturing Practices grade). We also investigated whether we could observe binding of 99mTc-fucoidan to human thrombi ex vivo and in vivo. In ten healthy volunteers, conjugate whole-body scans were performed up to 24 h following intravenous injection of 99mTc-fucoidan (370 MBq). Moreover, 99mTc-fucoidan uptake in ex vivo human thrombi (n = 11) was measured by gamma counting. Additionally, three patients with a newly diagnosed deep vein thrombosis (DVT) were subjected to 99mTc-fucoidan SPECT/CT imaging. Results 99mTc-fucoidan was well tolerated in all participants without any drug-related adverse events. The total-body absorbed dose in males was comparable to females (0.012 ± 0.004 vs. 0.011 ± 0.005 mSv/MBq; p = 0.97). Gamma counting experiments demonstrated binding of tracer to ex vivo human thrombi that was 16% lower after blocking with a natural P-selectin ligand, Sialyl Lewis X. 99mTc-fucoidan demonstrated specific uptake at the thrombus site in one out of three scanned patients with DVT. Conclusions 99mTc-Fucoidan has a favorable biodistribution and safety profile. 99mTc-fucoidan exhibited specific binding to human thrombi in both in vivo and ex vivo settings. Nonetheless, the in vivo results do not support further clinical investigation of 99mTc-fucoidan as an imaging modality for DVT. Other clinical implementations of a technetium− 99m-labeled P-selectin tracer should be considered. Trial registration: Clinicaltrials,NCT03422055.Registered 01/15/2018. URL: https://clinicaltrials.gov/study/NCT03422055 Landelijk Trial Register, NL7739. Registered 4/2/2019 . https://onderzoekmetmensen.nl/en/trial/26785https://doi.org/10.1186/s13550-024-01173-8DosimetrySPECTThrombusP-selectinFucoidan |
| spellingShingle | Reindert F. Oostveen Kang H. Zheng Yannick Kaiser Nick S. Nurmohamed Jeffrey Kroon Tim C. de Wit Edwin Poel Joel Aerts Francois Rouzet Erik S. G. Stroes Didier Letourneur Hein J. Verberne Cédric Chauvierre Mia R. Ståhle First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin EJNMMI Research Dosimetry SPECT Thrombus P-selectin Fucoidan |
| title | First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin |
| title_full | First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin |
| title_fullStr | First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin |
| title_full_unstemmed | First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin |
| title_short | First-in-human study of 99mTc-labeled fucoidan, a SPECT tracer targeting P-selectin |
| title_sort | first in human study of 99mtc labeled fucoidan a spect tracer targeting p selectin |
| topic | Dosimetry SPECT Thrombus P-selectin Fucoidan |
| url | https://doi.org/10.1186/s13550-024-01173-8 |
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