PT  - JOURNAL ARTICLE
AU  - Denoyer, Delphine
AU  - Lobachevsky, Pavel
AU  - Jackson, Price
AU  - Thompson, Mick
AU  - Martin, Olga A.
AU  - Hicks, Rodney J.
TI  - Analysis of <sup>177</sup>Lu-DOTA-Octreotate Therapy–Induced DNA Damage in Peripheral Blood Lymphocytes of Patients with Neuroendocrine Tumors
AID  - 10.2967/jnumed.114.145581
DP  - 2015 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 505--511
VI  - 56
IP  - 4
4099  - http://jnm.snmjournals.org/content/56/4/505.short
4100  - http://jnm.snmjournals.org/content/56/4/505.full
SO  - J Nucl Med2015 Apr 01; 56
AB  - Ionizing radiation–induced DNA double-strand breaks (DSBs) can lead to cell death, genome instability, and carcinogenesis. Immunofluorescence detection of phosphorylated histone variant H2AX (γ‐H2AX) is a reliable and sensitive technique to monitor external-beam ionizing radiation–induced DSBs in peripheral blood lymphocytes (PBLs). Here, we investigated whether γ-H2AX could be used as an in vivo marker to assess normal-tissue toxicity after extended internal irradiation with 177Lu-DOTA-octreotate (LuTate) peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors. Methods: We analyzed the kinetics of γ-H2AX foci in PBLs of 11 patients undergoing PRRT. The number of γ-H2AX foci was determined before and up to 72 h after treatment. These values were compared with the estimated absorbed dose to blood, spleen, bone marrow, and tumor and with subsequent PBL reduction. Results: The decrease in 177Lu activity in blood with time followed a biexponential kinetic pattern, with approximately 90% of circulating activity in blood cleared within 2 h. Absorbed dose to blood, but not to spleen or bone marrow, correlated with the administered 177Lu activity. PRRT increased γ-H2AX foci in lymphocytes in all patients, relative to pretherapy values. The response varied significantly between patients, but the average number of foci indicated a general trend toward an increase at 0.5–4 h with a subsequent decrease by 24–72 h after treatment. The peak number of foci correlated with the absorbed dose to tumor and bone marrow and the extent of PBL reduction. Conclusion: γ-H2AX can be exploited in the LuTate PRRT as a biomarker of PBL cytotoxicity. Long-term follow-up studies investigating whether elevated residual γ-H2AX values are associated with acute myelotoxicity and secondary blood malignancy may be worthwhile.