Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions
Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. Fo...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-09-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558609800389 |
| _version_ | 1819202836317077504 |
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| author | Moritz Palmowski Peter Peschke Jochen Huppert Peter Hauff Michael Reinhardt Mathias Maurer Christian P. Karger Michael Scholz Wolfhard Semmler Peter E. Huber Fabian M. Kiessling |
| author_facet | Moritz Palmowski Peter Peschke Jochen Huppert Peter Hauff Michael Reinhardt Mathias Maurer Christian P. Karger Michael Scholz Wolfhard Semmler Peter E. Huber Fabian M. Kiessling |
| author_sort | Moritz Palmowski |
| collection | DOAJ |
| description | Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1) and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy) was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens. |
| first_indexed | 2024-12-23T04:10:21Z |
| format | Article |
| id | doaj.art-03f6a596c6de4cc2a19ad9ab9678a831 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-23T04:10:21Z |
| publishDate | 2009-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-03f6a596c6de4cc2a19ad9ab9678a8312022-12-21T18:00:31ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022009-09-0111985686310.1593/neo.09540Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon IonsMoritz Palmowski0Peter Peschke1Jochen Huppert2Peter Hauff3Michael Reinhardt4Mathias Maurer5Christian P. Karger6Michael Scholz7Wolfhard Semmler8Peter E. Huber9Fabian M. Kiessling10Institute of Experimental Molecular Imaging, RWTH-Aachen University, Aachen, GermanyDepartment of Radiation Oncology, German Cancer Research Center and University Hospital Center, Heidelberg, GermanyMedical Physics in Radiology, German Cancer Research Center, Heidelberg, GermanyGlobal Drug Discovery, Bayer Schering Pharma AG, Berlin, GermanyGlobal Drug Discovery, Bayer Schering Pharma AG, Berlin, GermanyDepartment of Neurology, Erlangen University, Erlangen, GermanyMedical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg, GermanyGesellschaft fur Schwerionenforschung (GSI), Darmstadt, GermanyMedical Physics in Radiology, German Cancer Research Center, Heidelberg, GermanyDepartment of Radiation Oncology, German Cancer Research Center and University Hospital Center, Heidelberg, GermanyInstitute of Experimental Molecular Imaging, RWTH-Aachen University, Aachen, GermanyIndividualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1) and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy) was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.http://www.sciencedirect.com/science/article/pii/S1476558609800389 |
| spellingShingle | Moritz Palmowski Peter Peschke Jochen Huppert Peter Hauff Michael Reinhardt Mathias Maurer Christian P. Karger Michael Scholz Wolfhard Semmler Peter E. Huber Fabian M. Kiessling Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions Neoplasia: An International Journal for Oncology Research |
| title | Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions |
| title_full | Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions |
| title_fullStr | Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions |
| title_full_unstemmed | Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions |
| title_short | Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions |
| title_sort | molecular ultrasound imaging of early vascular response in prostate tumors irradiated with carbon ions |
| url | http://www.sciencedirect.com/science/article/pii/S1476558609800389 |
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