Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer

Bart Cornelissen, Sarah Able, Christiana Kartsonaki, Veerle Kersemans, P Danny Allen, Federica Cavallo, Jean-Baptiste Cazier, Manuela Iezzi, James Knight, Ruth Muschel, Sean Smart, Katherine A Vallis

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


UNLABELLED: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)2026-31
Number of pages6
JournalJournal of Nuclear Medicine
Issue number12
Publication statusPublished - Dec 2014


  • Animals
  • DNA Damage
  • Disease Progression
  • Female
  • Image Processing, Computer-Assisted
  • Immunoconjugates
  • Magnetic Resonance Imaging
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Precancerous Conditions
  • Radiopharmaceuticals
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon


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