Reply to: Determinants of 131I radiation dose to thyroid follicular cells

Abstract

We thank Dr. Eterovic and colleagues for their interest and comments. Our work was aimed at showing the ability of the Monte Carlo code “CELLDOSE” to assess electron dose to specific cells in a complex environment [1]. This approach can be of considerable interest for comparing different radiopharmaceuticals as therapy agents in oncology. Eterovic et al. used the EGS5 code, with a predefined energy cut-off of 1 keV [2]. Our track structure code follows all primary and secondary electrons down to 7.4 eV (i.e. below the first ionisation potential of the water molecule ≅ 12.6 eV) [3]. This makes “CELLDOSE” a valuable tool to calculate energy deposited at the tissue, cellular as well as sub-cellular scale. We used a model of normal thyroid tissue as an example. The geometrical model assumed spherical thyroid follicles of 170 μm diameter with a cell height of 10 μm. Neighbouring follicles are 4 μm apart. Based on the specific geometry presented, it is found that when the average I electron dose to thyroid tissue is 1 Gy, the dose to the colloidal matter is 1.168 Gy, the dose specifically received by thyroid cells is 0.982 Gy and the dose to the inter-follicular tissue is 0.895 Gy [1]. Eterovic and colleagues suggest that the thyroid cell dose we found is overestimated because of small follicle diameter and a packing of spheres based on the simple cubic model [4]. We fully agree that thyroid follicles may vary in size according to age and pathological conditions. The follicle size we used is compatible with the average for normal thyroid [5]. In a recent study, Faggiano et al. found an average diameter for thyroid follicles of 171 μm in adults and smaller values in children <12 years [6]. Of course, average diameter as seen on a single cut is an underestimation and data from full 3-D evaluation of thyroid tissue are lacking. Both our simulation and that of Eterovic have considered thyroid follicles as spherical [1, 2]. Thyroid follicles might not be truly spherical. However, it should not be forgotten that many of the aspects seen in histology can be influenced by the fixation and water extraction procedure during sample preparation. The amount of connective and vascular inter-follicular tissue should also be variable and should probably increase in pathological thyroid states in which inflammation plays an important role. We would like to point out that our model for follicles’ arrangement (follicles of 170 μm diameter in a cube with a side of 174 μm) leads to a volume occupied by follicles of 48.8% and not 42% as stated by Eterovic and colleagues. This suggests that new calculations based on the right volumes should allow the authors to obtain results even closer to ours. Eterovic et al. propose a model where follicles would occupy 90% of the tissue space, yet composed of spherical follicles of identical size [2, 4]. However, this assumption is somewhat surprising since it is well known from crystallography data and from mathematical approaches that, whatever the arrangement, the maximum density of spheres which can be achieved is 74% or d 1⁄4 p 3 ffiffi