Reply: ¹³¹I Radiation Dose Distribution in Metastases of Thyroid Carcinoma

REPLY: We thank Dr. Eterović and colleagues for their interest in our work. Our study on the distribution of the electron dose of ¹³¹I in isolated spheres of various sizes was not specifically referring to micrometastases of thyroid cancer and was not referring at all to normal thyroid tissue (1). ¹³¹I can be used for targeted radiotherapy using a variety of ligands (2), such as ¹³¹I-metaiodobenzylguanidine and ¹³¹I-labeled anti-CD20 antibody. We showed that, even in cases of homogeneous ¹³¹I distribution, the dose received by tumor cells within micrometastases will depend on a number of variables. For example, in a micrometastasis of 500-μm radius, the outermost shell layer would receive only two thirds of the average dose, and half that at the center (1). Also, as micrometastases become smaller, a higher radioactive concentration is necessary to achieve the same dose, because a larger part of the energy escapes from the metastases. A radioiodine concentration that delivers a dose of 100 Gy to a micrometastasis of 2,500-μm radius would deliver only 10 Gy in a cluster of 50-μm radius (1). These data, as we explained, assume a homogeneous distribution of ¹³¹I, and of course, heterogeneity in isotope distribution would affect dose distribution. Even for a long-range isotope such as ¹³¹I, the dose to a specific cell in small clusters can vary depending on whether this cell has retained the radioligand and on the subcellular distribution of ¹³¹I (3,4).

¹³¹I has an important role in the treatment of metastatic differentiated thyroid cancer and should indeed be applied early, before major heterogeneity in ¹³¹I uptake and distribution occurs (5).

Within micrometastases from thyroid cancer, the distribution of ¹³¹I should be variable depending on histology (papillary vs. follicular vs. Hürthle cell cancer) and also probably on the location (lymph node, lung, bone). For the most common variety, papillary thyroid cancer, the distribution of iodine should also be very variable depending on the subtype. Although iodine is bound to thyroglobulin and localized mostly in the extracellular compartment, its distribution is rather disorganized. Most often, there is no clear evidence that micrometastases of papillary cancer show a colloidal follicular structure as is present in normal tissue. It would be interesting to use microautoradiography or secondary ion mass spectrometry to assess the distribution of radioiodine or of stable iodine, as we showed for other models (6).

In conclusion, although our findings relating to the impact of the size of micrometastases and cell position would probably also apply to micrometastases of thyroid cancer; modeling the precise dose distribution in this situation would need knowledge of the heterogeneity using information from microscopic imaging studies.

We appreciate that the authors will comment on another work we recently published (7), and we would be pleased to answer those comments.