Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer.
A prominent feature of many human cancers is oncogene-driven activation of the DNA damage response (DDR) during early tumorigenesis. It has been shown previously that noninvasive imaging of the phosphorylated histone H2A variant H2AX, γH2AX, a DNA damage signaling protein, is possible using (111)In-...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Society of Nuclear Medicine
2014
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| _version_ | 1797078073103876096 |
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| author | Cornelissen, B Able, S Kartsonaki, C Kersemans, V Allen, P Cavallo, F Cazier, J Iezzi, M Knight, J Muschel, R Smart, S Vallis, K |
| author_facet | Cornelissen, B Able, S Kartsonaki, C Kersemans, V Allen, P Cavallo, F Cazier, J Iezzi, M Knight, J Muschel, R Smart, S Vallis, K |
| author_sort | Cornelissen, B |
| collection | OXFORD |
| description | A prominent feature of many human cancers is oncogene-driven activation of the DNA damage response (DDR) during early tumorigenesis. It has been shown previously that noninvasive imaging of the phosphorylated histone H2A variant H2AX, γH2AX, a DNA damage signaling protein, is possible using (111)In-labeled anti-γH2AX antibody conjugated to the cell-penetrating peptide transactivator of transcription (TAT). The purpose of this study was to investigate whether (111)In-anti-γH2AX-TAT detects the DDR during mammary oncogenesis in BALB-neuT mice.Mammary fat pads from BALB-neuT and wild-type mice (age, 40-106 d) were immunostained for γH2AX. (111)In-anti-γH2AX-TAT or a control probe was administered intravenously to BALB-neuT mice. SPECT was performed weekly and compared with tumor detection using palpation and dynamic contrast-enhanced MR imaging.γH2AX expression was elevated in hyperplastic lesions in the mammary fat pads of BALB-neuT mice aged 76-106 d, compared with normal fat pads from younger mice and carcinomas from older mice (13.5 ± 1.2 γH2AX foci/cell vs. 5.2 ± 1.5 [P < 0.05] and 3.4 ± 1.1 [P < 0.001], respectively). Serial SPECT imaging revealed a 2.5-fold increase in (111)In-anti-γH2AX-TAT accumulation in the mammary fat pads of mice aged 76-106 d, compared with control probe (P = 0.01). The median time to detection of neoplastic lesions by (111)In-anti-γH2AX-TAT (defined as >5% injected dose per gram of tissue) was 96 d, compared with 120 and 131 d for dynamic contrast-enhanced MR imaging and palpation, respectively (P < 0.001).DDR imaging using (111)In-anti-γH2AX-TAT identified mammary tumors significantly earlier than MR imaging. Imaging the DDR holds promise for the detection of preneoplasia and as a technique for screening cancer-prone individuals. |
| first_indexed | 2024-03-07T00:27:14Z |
| format | Journal article |
| id | oxford-uuid:7e8e9607-5928-454d-b3eb-fbcdd10a2085 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:27:14Z |
| publishDate | 2014 |
| publisher | Society of Nuclear Medicine |
| record_format | dspace |
| spelling | oxford-uuid:7e8e9607-5928-454d-b3eb-fbcdd10a20852022-03-26T21:10:49ZImaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7e8e9607-5928-454d-b3eb-fbcdd10a2085EnglishSymplectic Elements at OxfordSociety of Nuclear Medicine2014Cornelissen, BAble, SKartsonaki, CKersemans, VAllen, PCavallo, FCazier, JIezzi, MKnight, JMuschel, RSmart, SVallis, KA prominent feature of many human cancers is oncogene-driven activation of the DNA damage response (DDR) during early tumorigenesis. It has been shown previously that noninvasive imaging of the phosphorylated histone H2A variant H2AX, γH2AX, a DNA damage signaling protein, is possible using (111)In-labeled anti-γH2AX antibody conjugated to the cell-penetrating peptide transactivator of transcription (TAT). The purpose of this study was to investigate whether (111)In-anti-γH2AX-TAT detects the DDR during mammary oncogenesis in BALB-neuT mice.Mammary fat pads from BALB-neuT and wild-type mice (age, 40-106 d) were immunostained for γH2AX. (111)In-anti-γH2AX-TAT or a control probe was administered intravenously to BALB-neuT mice. SPECT was performed weekly and compared with tumor detection using palpation and dynamic contrast-enhanced MR imaging.γH2AX expression was elevated in hyperplastic lesions in the mammary fat pads of BALB-neuT mice aged 76-106 d, compared with normal fat pads from younger mice and carcinomas from older mice (13.5 ± 1.2 γH2AX foci/cell vs. 5.2 ± 1.5 [P < 0.05] and 3.4 ± 1.1 [P < 0.001], respectively). Serial SPECT imaging revealed a 2.5-fold increase in (111)In-anti-γH2AX-TAT accumulation in the mammary fat pads of mice aged 76-106 d, compared with control probe (P = 0.01). The median time to detection of neoplastic lesions by (111)In-anti-γH2AX-TAT (defined as >5% injected dose per gram of tissue) was 96 d, compared with 120 and 131 d for dynamic contrast-enhanced MR imaging and palpation, respectively (P < 0.001).DDR imaging using (111)In-anti-γH2AX-TAT identified mammary tumors significantly earlier than MR imaging. Imaging the DDR holds promise for the detection of preneoplasia and as a technique for screening cancer-prone individuals. |
| spellingShingle | Cornelissen, B Able, S Kartsonaki, C Kersemans, V Allen, P Cavallo, F Cazier, J Iezzi, M Knight, J Muschel, R Smart, S Vallis, K Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. |
| title | Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. |
| title_full | Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. |
| title_fullStr | Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. |
| title_full_unstemmed | Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. |
| title_short | Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. |
| title_sort | imaging dna damage allows detection of preneoplasia in the balb neut model of breast cancer |
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