Abstract
Recently, Gulec et al. presented the results of their clinical and quantitative analysis of 124I positron emission tomography/computed tomography (PET/CT) in patients with differentiated thyroid cancer (DTC) in this journal (1). They concluded from their prospective study that “(124)I PET/CT is a valuable clinical imaging tool/agent in extent of disease evaluation.”
In our opinion, it is of great importance to question whether this strong conclusion holds for a specific subgroup of the included patients, namely patients suspected to have recurrent disease based on increased thyroglobulin (Tg) levels but with a negative neck ultrasound. This group is of special interest, as currently no diagnostic modality is able to predict adequate uptake and benefit of treatment with radioactive iodine in tumor locations reliably. Diagnostic 131I whole-body scintigraphy (WBS) has a low sensitivity and is therefore no longer recommended (2,3).
The study by Gulec et al. included a mixed population of patients who were directly post thyroidectomy and thus less likely to have distant metastasis (n = 8), and patients with suspicion of metastatic disease based on increased Tg levels (n = 7) (1). Analyzing this latter group specifically, 4/7 124I PET/CTs were false negative, resulting in a sensitivity of 124I PET/CT of only 57% [confidence interval 18–90%]. This means that based on a negative 124I PET/CT, nearly half of the patients are considered as having dedifferentiated metastatic DTC, while in fact treatment with 131I would have resulted in a positive post-therapy scan.
This is in line with the results of our recently published study (4). We aimed to include 100 patients with suspicion of recurrence based on an increased Tg level, and planned for a therapeutic dose of 131I in a prospective multicenter diagnostic cohort study. Based on a predefined stopping rule, the study was preliminary terminated because in 5/17 included patients the 124I PET/CT was false negative compared with the 131I post-therapeutic 131I WBS. The sensitivity of 124I PET/CT in our study was 44%.
As more extensively discussed in our study, several factors might be the cause of the disappointing sensitivity of 124I PET/CT for this application. First, in our study, the method of preparation with recombinant human thyrotropin (rhTSH) as opposed to thyroid hormone withdrawal for the 131I therapy might lead to differences in iodine uptake and therefore to false negative 124I PET/CT scans. Second, the diagnostic dose of 74 MBq 124I (2 mCi) might be too low in comparison with the therapeutic doses of 131I (5.5–7.4 Gbq [150–200 mCi]) to reach a similar sensitivity (5,6).
The decision to treat with 131I, or to decide that a patient is iodine refractory, is crucial for patients with metastatic or recurrent DTC because 131I is the most potent treatment modality for these patients. The use of 124I PET/CT to make this decision, with an estimated patient-based sensitivity of 44–57%, would result in excluding about half of the patients from a potentially beneficial treatment.
In conclusion, 124I PET/CT as applied in the study by Gulec et al. (1) and in our own study can lead to false-negative results for patients with suspected recurrent DTC, and should therefore not yet be applied for treatment decisions in regular care.