[18F]PARPi Imaging Is Not Affected by HPV Status In Vitro
Background. Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including γH2AX, RAD51, and PARP1. Moreover, the role of [18F]PARPi as...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2021-01-01
|
| Series: | Molecular Imaging |
| Online Access: | http://dx.doi.org/10.1155/2021/6641397 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841561843003293696 |
|---|---|
| author | Navjot Guru Paula Demétrio De Souza França Giacomo Pirovano Cien Huang Snehal G. Patel Thomas Reiner |
| author_facet | Navjot Guru Paula Demétrio De Souza França Giacomo Pirovano Cien Huang Snehal G. Patel Thomas Reiner |
| author_sort | Navjot Guru |
| collection | DOAJ |
| description | Background. Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including γH2AX, RAD51, and PARP1. Moreover, the role of [18F]PARPi as a broadly applicable imaging tool for head and neck carcinomas is investigated. Methods. HPV-positive and HPV-negative cell lines were used to evaluate the γH2AX, RAD51, and PARP1 expression with immunoblotting and immunofluorescence. Effects of external beam ionizing radiation were investigated in vitro, and survival was investigated via colony-formation assay. [18F]PARPi uptake experiments were performed on HPV-negative and HPV-positive cell lines to quantify PARP1 expression. PARP1 IHC and γH2AX foci were quantified using patient-derived oropharyngeal tumor specimens. Results. Differences in DNA repair were detected, showing higher RAD51 and γH2AX expression in HPV-positive cell lines. Clonogenic assays confirm HPV-positive cell lines to be significantly more radiosensitive. PARP1 expression levels were similar, irrespective of HPV status. Consequently, [18F]PARPi uptake assays demonstrated that this tracer is internalized in cell lines independently from their HPV status. Conclusion. The HPV status, often used clinically to stratify patients, did not affect PARP1 levels, suggesting that PARP imaging can be performed in both HPV-positive and HPV-negative patients. This study confirms that the PET imaging agent [18F]PARPi could serve as a general clinical tool for oropharyngeal cancer patients. |
| format | Article |
| id | doaj-art-345caf3642574dcd81c2a0e72746fd77 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-345caf3642574dcd81c2a0e72746fd772025-01-03T01:22:57ZengSAGE PublishingMolecular Imaging1536-01212021-01-01202110.1155/2021/66413976641397[18F]PARPi Imaging Is Not Affected by HPV Status In VitroNavjot Guru0Paula Demétrio De Souza França1Giacomo Pirovano2Cien Huang3Snehal G. Patel4Thomas Reiner5Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USADepartment of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USADepartment of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USADepartment of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USADepartment of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USADepartment of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USABackground. Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including γH2AX, RAD51, and PARP1. Moreover, the role of [18F]PARPi as a broadly applicable imaging tool for head and neck carcinomas is investigated. Methods. HPV-positive and HPV-negative cell lines were used to evaluate the γH2AX, RAD51, and PARP1 expression with immunoblotting and immunofluorescence. Effects of external beam ionizing radiation were investigated in vitro, and survival was investigated via colony-formation assay. [18F]PARPi uptake experiments were performed on HPV-negative and HPV-positive cell lines to quantify PARP1 expression. PARP1 IHC and γH2AX foci were quantified using patient-derived oropharyngeal tumor specimens. Results. Differences in DNA repair were detected, showing higher RAD51 and γH2AX expression in HPV-positive cell lines. Clonogenic assays confirm HPV-positive cell lines to be significantly more radiosensitive. PARP1 expression levels were similar, irrespective of HPV status. Consequently, [18F]PARPi uptake assays demonstrated that this tracer is internalized in cell lines independently from their HPV status. Conclusion. The HPV status, often used clinically to stratify patients, did not affect PARP1 levels, suggesting that PARP imaging can be performed in both HPV-positive and HPV-negative patients. This study confirms that the PET imaging agent [18F]PARPi could serve as a general clinical tool for oropharyngeal cancer patients.http://dx.doi.org/10.1155/2021/6641397 |
| spellingShingle | Navjot Guru Paula Demétrio De Souza França Giacomo Pirovano Cien Huang Snehal G. Patel Thomas Reiner [18F]PARPi Imaging Is Not Affected by HPV Status In Vitro Molecular Imaging |
| title | [18F]PARPi Imaging Is Not Affected by HPV Status In Vitro |
| title_full | [18F]PARPi Imaging Is Not Affected by HPV Status In Vitro |
| title_fullStr | [18F]PARPi Imaging Is Not Affected by HPV Status In Vitro |
| title_full_unstemmed | [18F]PARPi Imaging Is Not Affected by HPV Status In Vitro |
| title_short | [18F]PARPi Imaging Is Not Affected by HPV Status In Vitro |
| title_sort | 18f parpi imaging is not affected by hpv status in vitro |
| url | http://dx.doi.org/10.1155/2021/6641397 |
| work_keys_str_mv | AT navjotguru 18fparpiimagingisnotaffectedbyhpvstatusinvitro AT paulademetriodesouzafranca 18fparpiimagingisnotaffectedbyhpvstatusinvitro AT giacomopirovano 18fparpiimagingisnotaffectedbyhpvstatusinvitro AT cienhuang 18fparpiimagingisnotaffectedbyhpvstatusinvitro AT snehalgpatel 18fparpiimagingisnotaffectedbyhpvstatusinvitro AT thomasreiner 18fparpiimagingisnotaffectedbyhpvstatusinvitro |