Endocrine Abstracts

The 68Ge/68Ga generator has the potential to greatly expand positron emission tomography (PET) imaging to benefit more patients, by allowing many PET applications in hospitals without immediate access to cyclotrons and costly radiochemistry facilities. It is often suggested that ‘68Ga is the new 99mTc,’ drawing parallels with conventional radiopharmacy practice where radiopharmaceuticals are prepared with little more complex equipment than a syr...

Background: The sodium/iodide symporter (NIS) frequently shows diminished targeting to the plasma membrane (PM) in differentiated thyroid cancer, resulting in suboptimal radioiodine treatment and poor prognosis. However, the mechanisms which govern the endocytosis of NIS away from the PM – its sole site of transport activity – are ill-defined, and may be of direct therapeutic potential. We previously showed that the proto-oncogene PBF binds NIS and enhances its inter...

Introduction: New drug approaches are urgently required to improve radioiodide (RAI) uptake for efficient ablation of thyroid cancer cells in RAI-refractory disease. Employing high-throughput screening of FDA-approved compounds we recently identified drugs capable of robust induction of sodium iodide symporter (NIS) activity to promote RAI uptake1. In particular, a leading drug candidate – the well-established anti-alcoholism drug disulfiram (DSF) – had no...

Background: Diminished sodium iodide symporter (NIS) activity at the plasma membrane (PM) is frequently associated with suboptimal radioiodide (RAI) uptake and poor prognosis in differentiated thyroid cancer (DTC). Endocytosis is a key determinant of symporter activity, with our recent study demonstrating specific interaction of NIS with Adaptor Protein 2 (AP2) – a central player in endocytosis. Here, our objective was to determine whether NIS endocytosis...

Introduction: New approaches to improve radioiodide (RAI) uptake are urgently required in RAI-refractory thyroid cancer. We previously identified disulfiram as a leading candidate to induce sodium iodide symporter (NIS) activity and promote RAI uptake. In vivo, DSF is metabolised to diethyldithiocarbamate (DDC) which binds metal ions. Here, we aimed to gain a mechanistic understanding of how DSF and it’s related metabolite Cu(DDC)2 imp...

Background: New drug approaches are urgently needed that enhance radioiodide (RAI) uptake leading to efficient ablation of thyroid cancer, especially in RAI-refractory disease. We recently utilised high-throughput screening and identified FDA-approved compounds that induce sodium iodide symporter (NIS) function to enhance iodide uptake, including the proteasomal/ VCP inhibitor disulfiram. In vivo, disulfiram is rapidly metabolized to diethyldithiocarbamate (DDC), whic...