REVIEW  NUCLEAR MEDICINE IN PRECISION ONCOLOGY 

The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2020 September;64(3):250-64

DOI: 10.23736/S1824-4785.20.03264-1

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

Managing radioiodine refractory thyroid cancer: the role of dosimetry and redifferentiation on subsequent I-131 therapy

Maaike DOTINGA ¹ ✉, Dennis VRIENS ¹, Floris van VELDEN ¹, Linda HEIJMEN ¹, James NAGARAJAH ^{2, 3}, Rodney HICKS ⁴, Ellen KAPITEIJN ⁵, Lioe-Fee de GEUS-OEI ^{1, 6}

¹ Section of Nuclear Medicine, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; ² Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; ³ Department of Nuclear Medicine, Technical University Munich, Munich, Germany; ⁴ Department of Molecular Imaging, Peter MacCallum Cancer Center, Melbourne, VIC, Australia; ⁵ Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; ⁶ Biomedical Photonic Imaging Group, University of Twente, Enschede, the Netherlands

Poor responses to iodine-131 (I-131) therapy can relate to either low iodine uptake and retention in thyroid cancer cells or to increased radioresistance. Both mechanisms are currently termed radioactive iodine (RAI)-refractory (RAI-R) thyroid cancer but the first reflects unsuitability for I-131 therapy that can be evaluated in advance of treatment, whereas the other can only be identified post hoc. Management of both represents a considerable challenge in clinical practice as failure of I-131 therapy, the most effective treatment of metastatic thyroid cancer, is associated with a poor overall prognosis. The development of targeted therapies has shown substantial promise in the treatment of RAI-R thyroid cancer in progressive patients. Recent studies show that selective tyrosine kinase inhibitors (TKIs) targeting B-type rapidly accelerated fibrosarcoma kinase (BRAF) and mitogen-activated protein kinase (MEK) can be used as redifferentiation agents to re-induce RAI uptake, thereby (re)enabling I-131 therapy. The use of dosimetry prior- and post-TKI treatment can assist in quantifying RAI uptake and improve identification of patients that will benefit from I-131 therapy. It also potentially offers the prospect of calculating individualized therapeutic administered activities to enhance efficacy and limit toxicity. In this review, we present an overview of the regulation of RAI uptake and clinically investigated redifferentiation agents, both reimbursed and in experimental setting, that induce renewed RAI uptake. We describe the role of dosimetry in redifferentiation and subsequent I-131 therapy in RAI-R thyroid cancer, explain different dosimetry approaches and discuss limitations and considerations in the field.

KEY WORDS: Radiometry; Thyroid neoplasms; Therapeutics