Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain
Purpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/4/861 |
| _version_ | 1797482136016519168 |
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| author | Marcus C. M. Stroet Erik de Blois Marion de Jong Yann Seimbille Laura Mezzanotte Clemens W. G. M. Löwik Kranthi M. Panth |
| author_facet | Marcus C. M. Stroet Erik de Blois Marion de Jong Yann Seimbille Laura Mezzanotte Clemens W. G. M. Löwik Kranthi M. Panth |
| author_sort | Marcus C. M. Stroet |
| collection | DOAJ |
| description | Purpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence imaging of both spontaneous and treatment-induced necrosis in murine breast cancer models. We simultaneously recorded [<sup>18</sup>F]FDG-PET and bioluminescence images for complementary detection of tumor viability. Results: We generated two albumin-binding IRDye800CW derivatives which were labeled with indium-111 with high radiochemical purity. Surprisingly, both albumin-binding NACAs had >10x higher in vitro binding towards dead cells. We selected [<sup>111</sup>In]<b>3</b> for in vivo experiments which showed higher dead cell binding in vitro and in vivo stability. The doxorubicin-treated tumors showed increased [<sup>111</sup>In]<b>3</b>-uptake (1.74 ± 0.08%ID/g after saline treatment, 2.25 ± 0.16%ID/g after doxorubicin treatment, <i>p</i> = 0.044) and decreased [<sup>18</sup>F]FDG-uptake (3.02 ± 0.51%ID/g after saline treatment, 1.79 ± 0.11%ID/g after doxorubicin treatment, <i>p</i> = 0.040), indicating therapy efficacy. Moreover, we detected increased [<sup>111</sup>In]<b>3-</b>uptake and tumor necrosis in more rapidly growing EMT6 tumors. Conclusions: Our albumin-binding NACA based on IRDye800CW facilitates tumor-necrosis imaging for assessment of therapy efficacy and aggressiveness in solid tumors using both fluorescence and SPECT imaging. |
| first_indexed | 2024-03-09T22:24:57Z |
| format | Article |
| id | doaj.art-508077bb62f741b7bbb113a2d6c15046 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:24:57Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-508077bb62f741b7bbb113a2d6c150462023-11-23T19:07:30ZengMDPI AGCancers2072-66942022-02-0114486110.3390/cancers14040861Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding DomainMarcus C. M. Stroet0Erik de Blois1Marion de Jong2Yann Seimbille3Laura Mezzanotte4Clemens W. G. M. Löwik5Kranthi M. Panth6Erasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsErasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsErasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsErasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsErasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsErasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsErasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsPurpose: To assess our improved NACA for the detection of tumor necrosis. Methods: We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence imaging of both spontaneous and treatment-induced necrosis in murine breast cancer models. We simultaneously recorded [<sup>18</sup>F]FDG-PET and bioluminescence images for complementary detection of tumor viability. Results: We generated two albumin-binding IRDye800CW derivatives which were labeled with indium-111 with high radiochemical purity. Surprisingly, both albumin-binding NACAs had >10x higher in vitro binding towards dead cells. We selected [<sup>111</sup>In]<b>3</b> for in vivo experiments which showed higher dead cell binding in vitro and in vivo stability. The doxorubicin-treated tumors showed increased [<sup>111</sup>In]<b>3</b>-uptake (1.74 ± 0.08%ID/g after saline treatment, 2.25 ± 0.16%ID/g after doxorubicin treatment, <i>p</i> = 0.044) and decreased [<sup>18</sup>F]FDG-uptake (3.02 ± 0.51%ID/g after saline treatment, 1.79 ± 0.11%ID/g after doxorubicin treatment, <i>p</i> = 0.040), indicating therapy efficacy. Moreover, we detected increased [<sup>111</sup>In]<b>3-</b>uptake and tumor necrosis in more rapidly growing EMT6 tumors. Conclusions: Our albumin-binding NACA based on IRDye800CW facilitates tumor-necrosis imaging for assessment of therapy efficacy and aggressiveness in solid tumors using both fluorescence and SPECT imaging.https://www.mdpi.com/2072-6694/14/4/861necrosis-avid contrast agentcyaninesmultimodal imagingtherapy efficacy |
| spellingShingle | Marcus C. M. Stroet Erik de Blois Marion de Jong Yann Seimbille Laura Mezzanotte Clemens W. G. M. Löwik Kranthi M. Panth Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain Cancers necrosis-avid contrast agent cyanines multimodal imaging therapy efficacy |
| title | Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain |
| title_full | Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain |
| title_fullStr | Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain |
| title_full_unstemmed | Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain |
| title_short | Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain |
| title_sort | improved multimodal tumor necrosis imaging with irdye800cw dota conjugated to an albumin binding domain |
| topic | necrosis-avid contrast agent cyanines multimodal imaging therapy efficacy |
| url | https://www.mdpi.com/2072-6694/14/4/861 |
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