Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer

Abstract

This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving I for thyroid remnant ablation or treatment of metastatic disease. The observed chromosomal damage was further converted to the estimates of whole-body dose to project the adverse side effects. Chromosomal aberration analysis was performed in 24 patients treated for the first time or after multiple courses. Blood samples were collected before treatment and 3 or 4 days after administration of 2-4 GBq of I. Both conventional cytogenetic and chromosome 2, 4 and 12 painting assays were used. To account for dose-rate effect, a dose-protraction factor was applied to calculate the whole-body dose. The mean dose was 0.62 Gy (95% CI: 0.44-0.77 Gy) in the subgroup of patients treated one time and 0.67 Gy (95% CI: 0.03-1.00 Gy) in re-treated patients. These dose estimates are about 1.7-fold higher than those disregarding the effect of exposure duration. In re-treated patients, the neglected dose-rate effect can result in underestimation of the cumulative whole-body dose by the factor ranging from 2.6 to 6.8. Elevated frequency of chromosomal aberrations observed in re-treated patients before radioiodine therapy allows estimation of a cumulative dose received from all previous treatments.

Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow-up study using multicolor FISH

“…Further studies are required to clarify whether or not the DNA damage inflicted in the adult stem cells by radioiodine therapy is the root cause for the ensuing chromosomal aberrations at enhanced levels in this patient. The current study indicates that the persistence of stable and unstable aberrations induced by RIT can be of use, not only in long-term monitoring of genomic instability, but also in predicting the absorbed dose by retrospective biodosimetry, as recently demonstrated by Khvostunov et al [ 20 ]. However, extreme caution is necessary when extrapolating the initial yield of stable aberrations to equate absorbed radiation dose when the therapeutic radiation exposure is high and non-uniform in nature.…”

“…Khvostunov et al [ 20 ] recently reported the yield of unstable and stable chromosomal aberrations in 24 differentiated thyroid cancer patients who were either treated for the first time or multiple times with radioiodine. In corroboration with our study, frequencies of both stable and unstable aberrations had increased considerably in these patients before and after radioiodine therapy when compared with the baseline frequencies reported in the literature.…”

Cytogenetic Damage Induced by Radioiodine Therapy: A Follow-Up Case Study

“…For Pat1, the whole-body dose after one RIT course ranged between 0.52 and 0.95 Gy for solid staining and between 0.57 and 0.75 Gy for FISH. The respective doses of Pat2 ranged between 0.25 and 0.57 Gy and was 0.10 Gy for FISH (one-course conventional data were published in [ 16 ]).…”

“…The CA yields induced by a single RIT identified by mFISH in both patients do not exceed the CA yields induced by in vitro irradiation received at doses of (0.25–0.5) Gy ( Figure 1 C). Accounting for the dose rate effect [ 16 ], these CA frequencies correspond to a dose of about 40 percent larger, i.e., (0.35–0.7) Gy. Therefore, rough estimates of the accumulated dose as a result of the RIT courses using mFISH data are (1.4–2.8) Gy for Pat1 and (0.7–1.4) Gy for Pat2.…”

“…Similarly, for Pat2, it was 9.09 and 10.3 CA/100 GEcells ( Table 2 ). As part of the model scenario of chronic exposure (G(T) = 0, α = 1.58 CA/100 cells, Gy −1 [ 16 ]), accounting for the age control [ 19 ], the accumulated dose is estimated at 2.1–3.2 Gy for Pat1 and 5.2–6.0 Gy for Pat2. This biodosimetric estimate is more accurate than the one based on the total administered activity, which is 0.55 and 11.1 Gy for Pat1 and Pat2, respectively (k D = 0.238 mGy/MBq [ 5 , 16 ]).…”