124 I PET/CT images from differentiated thyroid cancer patients were retrospectively analyzed to assess the relationship between absorbed radiation dose (AD) to lesions and their response after radioiodine therapy. Methods: Patients received serial 124 I PET/CT scans before and after their first radioiodine treatment. The pretherapy PET data were used to segment the lesion volumes and to predict the therapy-delivered ADs after administration of the therapeutic 131 I activity. The segmentation method's lower volume limit of determinability was a sphere of 0.80 mL, which classified the lesions into a known-volume group (.0.80 mL) or a small-volume group (#0.80 mL) with their respective average and minimum ADs. The posttherapy PET data were used to assess the lesion-based therapy success. In the known-volume group, the response rate was calculated on the basis of lesions that received average ADs above the generally accepted threshold of 85 Gy for metastases and 300 Gy for thyroid remnants (TRs) and was expressed as the percentage of completely responding lesions. In the small-volume group, the metastasis and TR responses were evaluated for 3 minimum-AD groups: 5 to 10 Gy (TR, 5 to 30 Gy), .10 to 85 Gy (TR, .30 to 300 Gy), and .85 Gy (TR, .300 Gy). Their response rates were calculated in terms of the percentage of completely responding lesions in each minimum-AD group. Results: In total, 59 lesions in 17 patients were amenable to reliable volume estimation. The response rates were 63%, 88%, and 90% for lymph node metastases (LMs), pulmonary metastases, and TRs, respectively. The response rates of 168 small lesions in 34 patients were more than 82% for LMs and more than 91% for TRs in each of the 3 minimum-AD groups; all small pulmonary metastases responded completely. Conclusion: In the known-volume group, the response rate for TRs matched well with historical data derived using 131 I scintigraphy imaging, whereas the response rate for LMs was not as high as expected, which may be explained by too short a follow-up time for a few LMs and a higher sensitivity of PET imaging. Small lesions were treated effectively, suggesting that they are considerably smaller than 0.80 mL. Radi oiodine therapy has been established in the management of differentiated thyroid cancer (DTC) after total thyroidectomy (except for patients at very low risk, such as those with papillary microcarcinoma). Radioiodine treatment is used primarily to eliminate tumor tissue, that is, locoregional lymph node metastases (LMs), distant metastases such as pulmonary metastases (PMs) and bone metastases (BMs), and secondarily to ablate thyroid remnants (TRs). In particular, the successful treatment of metastases is relevant because patients with metastases that completely respond have considerably higher survival rates than patients with incompletely responding metastases (1).The established quantity of radiation that mediates successful therapy is the absorbed radiation dose (AD) to lesions. Historically, the relationship between AD and response succe...