Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

Abstract

Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

Figure 1

Patients A and B were diagnosed with advanced ovarian cancer. Pretreatment F-18 FDG PET imaging successfully visualized multiple cancerous lesions in the neck and abdominal cavity. However, the imaging was not able to predict the therapeutic response to the subsequent chemotherapy. Patient A achieved complete remission after chemotherapy; however, patient B progressed to disease status after chemotherapy.

Figure 2

Patients A and B were diagnosed with thyroid cancer with pulmonary metastases (indicated by arrows) by pretreatment diagnostic CT imaging. Radioiodine imaging was able to forecast the therapeutic response to I-131 treatment. Patient A showed obvious uptake on radioiodine imaging and achieved complete remission after three I-131 treatments; however, patient B showed no radioiodine uptake on the imaging and progressed to disease status after I-131 treatment.

Figure 3

Flip-flop phenomenon of iodine and glucose avidity in thyroid cancer. Well-differentiated thyroid cancer has characteristics of the originating thyroid follicular cells, and therefore, the cancer cells can take up iodine, but not glucose. Therefore, the cancer lesions can be visualized on radioiodine imaging (blue box) but not on F-18 FDG PET imaging (red box). In contrast, poorly differentiated thyroid cancer does not have the characteristics of the originating thyroid follicular cells and has cancer hallmarks, and therefore, the cancer can take up glucose, but not iodine. Therefore, the cancer lesions can be visualized on F-18 FDG PET imaging, but not on radioiodine imaging.

Figure 4

Dosimetric assessment with multiple whole-body and SPECT images using a commercialized program. The retention time of each organ is obtained by imaging data with the images and the estimated absorbed doses for the organs and lesions are calculated using the OLINDA program.

Figure 5

Signaling pathways related to iodine avidity or glucose avidity by thyroid cancers. Well-differentiated thyroid cancer has less iodine avidity and greater glucose avidity than normal thyroid follicular cell by activity of MAPK kinase and PI3K-AKT pathways, which inhibit the expression of thyroid related genes and reinforce the expression of tumor promoting genes. The pathways become more active in poorly differentiated thyroid cancer compared to well-differentiated thyroid cancer and eventually it loses the iodine avidity and acquires glucose avidity. RTK: receptor tyrosine kinase.

Figure 6

Strategies of pharmacologic redifferentiation of radioiodine refractory thyroid cancer by intervening genetic and epigenetic alterations and dysregulated signaling pathways related to the cancer.