TY - JOUR T1 - Imaging DNA Damage Allows Detection of Preneoplasia in the BALB-<em>neu</em>T Model of Breast Cancer JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 2026 LP - 2031 DO - 10.2967/jnumed.114.142083 VL - 55 IS - 12 AU - Bart Cornelissen AU - Sarah Able AU - Christiana Kartsonaki AU - Veerle Kersemans AU - P. Danny Allen AU - Federica Cavallo AU - Jean-Baptiste Cazier AU - Manuela Iezzi AU - James Knight AU - Ruth Muschel AU - Sean Smart AU - Katherine A. Vallis Y1 - 2014/12/01 UR - http://jnm.snmjournals.org/content/55/12/2026.abstract N2 - 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 111In-labeled anti-γH2AX antibody conjugated to the cell-penetrating peptide transactivator of transcription (TAT). The purpose of this study was to investigate whether 111In-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. 111In-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 &lt; 0.05] and 3.4 ± 1.1 [P &lt; 0.001], respectively). Serial SPECT imaging revealed a 2.5-fold increase in 111In-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 111In-anti-γH2AX-TAT (defined as &gt;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 &lt; 0.001). Conclusion: DDR imaging using 111In-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. ER -