RT Journal Article SR Electronic T1 Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 743 OP 750 DO 10.2967/jnumed.119.232934 VO 61 IS 5 A1 O’Neill, Edward A1 Kersemans, Veerle A1 Allen, P. Danny A1 Terry, Samantha Y.A. A1 Torres, Julia Baguña A1 Mosley, Michael A1 Smart, Sean A1 Lee, Boon Quan A1 Falzone, Nadia A1 Vallis, Katherine A. A1 Konijnenberg, Mark W. A1 de Jong, Marion A1 Nonnekens, Julie A1 Cornelissen, Bart YR 2020 UL http://jnm.snmjournals.org/content/61/5/743.abstract AB Molecular radiotherapy using 177Lu-DOTATATE is a most effective treatment for somatostatin receptor–expressing neuroendocrine tumors. Despite its frequent and successful use in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery. On positive uptake on octreotide-based PET/SPECT imaging, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry, or radiobiologic and DNA damage effects in the tumor. Here, we visualized and quantified the extent of DNA damage response after 177Lu-DOTATATE therapy using SPECT imaging with 111In-anti-γH2AX-TAT. This work was a proof-of-principle study of this in vivo noninvasive biodosimeter with β-emitting therapeutic radiopharmaceuticals. Methods: Six cell lines were exposed to external-beam radiotherapy (EBRT) or 177Lu-DOTATATE, after which the number of γH2AX foci and the clonogenic survival were measured. Mice bearing CA20948 somatostatin receptor–positive tumor xenografts were treated with 177Lu-DOTATATE or sham-treated and coinjected with 111In-anti-γH2AX-TAT, 111In-IgG-TAT control, or vehicle. Results: Clonogenic survival after external-beam radiotherapy was cell-line–specific, indicating varying levels of intrinsic radiosensitivity. Regarding in vitro cell lines treated with 177Lu-DOTATATE, clonogenic survival decreased and γH2AX foci increased for cells expressing high levels of somatostatin receptor subtype 2. Ex vivo measurements revealed a partial correlation between 177Lu-DOTATATE uptake and γH2AX focus induction between different regions of CA20948 xenograft tumors, suggesting that different parts of the tumor may react differentially to 177Lu-DOTATATE irradiation. Conclusion: 111In-anti-γH2AX-TAT allows monitoring of DNA damage after 177Lu-DOTATATE therapy and reveals heterogeneous damage responses.