Cellular and molecular basis for thyroid cancer imaging in nuclear medicine

Abstract

Papillary and follicular thyroid carcinomas (well-differentiated forms) are the most common follicular cell-derived thyroid malignancies, while poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas (also poorly differentiated) are the less common ones. Papillary carcinomas are morphologically and genetically different from follicular carcinomas: the former are associated, in up to 70 % of cases, with BRAF or RAS point mutations or RET/PTC rearrangements; the latter carry the RAS point mutation or the PAX8/PPARgamma rearrangement. The poorly differentiated forms have abnormalities in the TP53 and the CTNNB1 genes. The best way to image thyroid cancer cells is to exploit the capability of normal follicular thyroid cells to concentrate iodine 131I through the sodium–iodine symporter. Iodine is necessary for the production of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Unfortunately, the cells of poorly differentiated carcinomas lose the capability to concentrate iodine; at the same time, their basal metabolism increases to satisfy the energy demands of highly proliferating cells. These cells require more glucose and a glucose analog, namely 18F-2-fluoro-2-deoxy-d-glucose (18FDG), is used in place of glucose to study their metabolism. The increased intake of glucose is mediated by a transmembrane transporter called glucose transporter-1 located on the cell membrane. The alternation of 131I and 18FDG uptake observed in thyroid tumors and their metastases is known as the “flip-flop” phenomenon. This review looks at the cellular and molecular mechanisms underlying thyroid cancer and thyroid cancer imaging.