Abstract
We appreciate the careful review of our manuscript by Dr. Kist et al. (1) in response to our recent publication in Thyroid (2). The authors draw attention to the false negative occurrences of 124I on a by-patient basis involving a subgroup of patients suspected of having recurrent disease based on increased thyroglobulin levels. This is a clinically important observation. However, there are a number of misinterpretations and inaccurate statements in their letter. (i) The number of false negative studies is three, not four. (ii) Despite their false negative status on 124I, these patients had nodular lung disease detected on computed tomography (CT) suspicious for recurrent disease in addition to increased thyroglobulin levels. (iii) Dr. Kist et al. state that “based on a negative 124I PET/CT, nearly half of the patients are considered as having dedifferentiated metastatic DTC.” Our study, however, clearly defines radioiodine-resistant disease as 124I (negative) 131I (negative) Fludeoxyglucose (positive) [see Table 1 of Gulec et al. (2)]. (iv) Dr. Kist et al. refer to our concluding statement, “124I PET/CT is a valuable clinical imaging tool/agent in extent of disease evaluation” as a “strong conclusion.” The statement is self-explanatory. 124I PET/CT is indeed a valuable tool. This does not necessarily equate with it having a “superb” sensitivity in all clinical scenarios. There are limitations to all diagnostic modalities. Their clinical use and value are appraised in an individual clinical context. 124I PET/CT has intrinsic limitations as do other radiopharmaceuticals using PET/CT technology.
It is of great interest that the false negative results in our study as well as others reported in the literature including the ones by Kist et al. (3) are most often reported in the lungs. All respective false negative cases in our study were performed under a protocol of thyroid hormone withdrawal; thus, a possible effect of recombinant human thyrotropin is not pertinent in our study. We compared 2 mCi 124I PET/CT and post therapy (>100 mCi) 131I planar imaging. We recognize and agree with Dr. Kist et al. that the 2 mCi administered activity is potentially one of the most important factors in lesion detection accuracy. Some possible explanations as to why lung lesions in particular (in our study) were not detected on 124I PET/CT involve PET/CT physics and radioiodine kinetics in the setting of decreased sodium-iodide symporter function present in metastatic lesions. Potential contributions of some of these factors to imaging performance were discussed in our study. First and foremost, PET/CT has a resolution limit of five to six millimeters (depending on the sophistication of the imaging system). Respiratory motion artifacts and partial volume effects are significant detriments of image quality. These effects are also manifest in planar imaging but may be less defining; in fact, respiratory motion in particular could produce a “paintbrush” effect in the final image formation, which may contribute to the diffuse lung activity seen on planar post therapy scans. Kinetic factors are also of importance including: (i) the complex decay profile of 124I, which creates artifactual high-energy gamma photons, which could contribute to background noise, and (ii) the relationship between the sodium-iodide symporter activity (altered in metastatic disease) and the elimination half-lives of respective radioisotopes (double in length with 131I versus 124I).
We do strongly believe that 124I PET/CT, despite its well-recognized limitations (not different from any other diagnostic tool), is a clinically valuable modality not only for imaging but also for lesion quantification/dosimetry. We do endorse its incorporation into the management of thyroid cancer in the appropriate clinical context. It should not be the sole determinant of treatment with radioiodine, as there are many other factors that come into play. We disagree that the limitations should preclude its application in clinical practice. To conclude otherwise and dismiss the modality would undermine the power and potential utilities of PET/CT and would be unjust.