Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment
Imaging tumors and their response to treatment could be a valuable biomarker toward early assessment of therapy in patients with cancer. Phosphatidylserine (PS) is confined to the inner leaflet of the plasma membrane in normal cells but is externalized on tumor vascular endothelial cells (ECs) and t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2013-06-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2012.00039 |
| _version_ | 1797288682002055168 |
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| author | Jian Gong Richard Archer Michael Brown Seth Fisher Connie Chang Matthew Peacock Christopher Hughes Bruce Freimark |
| author_facet | Jian Gong Richard Archer Michael Brown Seth Fisher Connie Chang Matthew Peacock Christopher Hughes Bruce Freimark |
| author_sort | Jian Gong |
| collection | DOAJ |
| description | Imaging tumors and their response to treatment could be a valuable biomarker toward early assessment of therapy in patients with cancer. Phosphatidylserine (PS) is confined to the inner leaflet of the plasma membrane in normal cells but is externalized on tumor vascular endothelial cells (ECs) and tumor cells, and PS exposure is further enhanced in response to radiation and chemotherapy. In the present study, we evaluated the potential of a PS-targeting human F(ab') 2 antibody fragment, PGN650, to detect exposure of PS in tumor-bearing mice. Tumor uptake of PGN650 was measured by near-infrared optical imaging in human tumor xenografts in immunodeficient mice. PGN650 specifically targeted tumors and was shown to target CD31-positive ECs and tumor cells. Tumor uptake of PGN650 was significantly higher in animals pretreated with docetaxel. The peak tumor to normal tissue (T/N) ratio of probe was observed at 24 hours postinjection of probe, and tumor binding was detected for at least 120 hours. In repeat dose studies, PGN650 uptake in tumors was significantly higher following pretreatment with docetaxel compared to baseline uptake prior to treatment. PGN650 may be a useful probe to detect PS exposed in tumors and to monitor enhanced PS exposure to optimize therapeutic agents to treat tumors. |
| first_indexed | 2024-03-07T18:53:01Z |
| format | Article |
| id | doaj.art-1396598d3c6c4f34ac6f8e34f0c3b49e |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2024-03-07T18:53:01Z |
| publishDate | 2013-06-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-1396598d3c6c4f34ac6f8e34f0c3b49e2024-03-02T01:01:14ZengSAGE PublicationsMolecular Imaging1536-01212013-06-011210.2310/7290.2012.0003910.2310_7290.2012.00039Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody FragmentJian GongRichard ArcherMichael BrownSeth FisherConnie ChangMatthew PeacockChristopher HughesBruce FreimarkImaging tumors and their response to treatment could be a valuable biomarker toward early assessment of therapy in patients with cancer. Phosphatidylserine (PS) is confined to the inner leaflet of the plasma membrane in normal cells but is externalized on tumor vascular endothelial cells (ECs) and tumor cells, and PS exposure is further enhanced in response to radiation and chemotherapy. In the present study, we evaluated the potential of a PS-targeting human F(ab') 2 antibody fragment, PGN650, to detect exposure of PS in tumor-bearing mice. Tumor uptake of PGN650 was measured by near-infrared optical imaging in human tumor xenografts in immunodeficient mice. PGN650 specifically targeted tumors and was shown to target CD31-positive ECs and tumor cells. Tumor uptake of PGN650 was significantly higher in animals pretreated with docetaxel. The peak tumor to normal tissue (T/N) ratio of probe was observed at 24 hours postinjection of probe, and tumor binding was detected for at least 120 hours. In repeat dose studies, PGN650 uptake in tumors was significantly higher following pretreatment with docetaxel compared to baseline uptake prior to treatment. PGN650 may be a useful probe to detect PS exposed in tumors and to monitor enhanced PS exposure to optimize therapeutic agents to treat tumors.https://doi.org/10.2310/7290.2012.00039 |
| spellingShingle | Jian Gong Richard Archer Michael Brown Seth Fisher Connie Chang Matthew Peacock Christopher Hughes Bruce Freimark Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment Molecular Imaging |
| title | Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment |
| title_full | Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment |
| title_fullStr | Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment |
| title_full_unstemmed | Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment |
| title_short | Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment |
| title_sort | measuring response to therapy by near infrared imaging of tumors using a phosphatidylserine targeting antibody fragment |
| url | https://doi.org/10.2310/7290.2012.00039 |
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