Theranostics With RAI Offer a Precision Approach to Treating Differentiated Thyroid Cancer

A theranostic approach to radioactive iodine therapy in thyroid cancer has become the standard of care and represents a more precise means of managing patients based on disease-specific features, according to a presentation on differentiated thyroid cancer management at the Society of Nuclear Medicine and Molecular Imaging 2019 Annual Meeting, held June 22-25, 2019, in Anaheim, California.

Amir H. Khandani, MD

A theranostic approach to radioactive iodine (RAI) therapy in thyroid cancer has become the standard of care and represents a more precise means of managing patients based on disease-specific features, according to a presentation on differentiated thyroid cancer management at the Society of Nuclear Medicine and Molecular Imaging 2019 Annual Meeting, held June 22-25, 2019, in Anaheim, California.1

“RAI is the original radiotheranostic and is still a moving target,” Amir H. Khandani, MD, associate professor of radiology and director of the Nuclear Medicine Residency/Fellowship program at the University of North Carolina at Chapel Hill School of Medicine, said during the presentation. “RAI therapy is personalized based on patient and disease factors, available information, and the nuclear medicine physician’s approach and experience, [and these] same principles apply to other radionuclide therapies.”

Ravinder K. Grewal, MD, nuclear medicine physician at Memorial Sloan Kettering Cancer Center (MSK) in New York City, reviewed updates to thyroid cancer staging in the 8th edition of the American Joint Committee on Cancer Staging Manual, which include raising the minimum age for stage III disease from 45 to 55 years. In one analysis, 23% of patients selected from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program who had papillary thyroid cancer (PTC) were downstaged from the previous edition. These changes in the staging system may help clinicians better determine which therapies are appropriate for PTC management on a case-by-case basis.2

“Patients with stage III, IVa, and IVb disease have a high risk of death from thyroid cancer,” said Grewal. She then detailed features of the disease that determine the updated staging for patients with differentiated thyroid cancer. She also pointed out that patients younger than 55 years can only have stage I or II disease by the 8th edition staging criteria (TABLE 1).1

Tailoring Therapy with RAI

Based on recommendations from R. Michael Tuttle, MD, and Mona M. Sabra, MD,3both from MSK, indications for postoperative RAI remnant ablation include a primary tumor >4 cm; gross extrathyroidal extension; distant metastases; large-volume cervical lymph node metastases; PTC, follicular thyroid cancer, or Hurthle cell cancer with vascular invasion; poorly differentiated thyroid cancer; inappropriately elevated postoperative thyroglobulin (Tg) levels; or a worrisome finding on radiologic imaging that might suggest metastasis. RAI ablation should not be used if all necessary diagnostic information is available, postoperative Tg is <1 ng/mL, and no other suspicion of persistent disease is present.1,3

Grewal detailed the treatment of patients by classifying them into 3 possible treatment cohorts: patients who have recently undergone thyroidectomy, patients with low-risk disease, and patients with high-risk disease.

She said that patients at MSK in the first group—those who recently underwent total thyroidectomy—may be recommended for radioiodine remnant ablation to remove residual metastatic tissue. These patients are given an injection of thyrotropin alfa (Thyrogen) to raise the level of thyroid-stimulating hormone to >30 mIU/L on days 1 and 2 as well as 1.5 mCi of iodine-123 on day 2. On day 3, diagnostic scans are performed to determine the amount of tissue remaining, and the patient is treated with the corresponding amount of iodine-131 (I-131).

The second group of patients treated at MSK, who are considered low risk, receive limited dosimetry. These patients are seen over 5 days, with thyrotropin alfa administered on days 1 and 2 as well as 5 mCi of I-131 on day 2. Diagnostic imaging is then performed on day 5.

The third group of patients fall into the high-risk category and receive full dosimetry. As in the prior groups, thyrotropin alfa is administered on days 1 and 2. On day 3, these patients are given 5 mCi of I-131 and undergo 3 whole-body sweeps. Days 4 through 6 involve whole-body radiation and diagnostic scans.

“The idea is to give the maximum-safe tolerated dose based on total body and blood clearance of 200 rads to blood, body retention less than 120 mCi at 48 hours, and 80 mCi in diffuse lung metastatic disease,” said Grewal. “There is no limit to a single dose, but it is typically less than 500 mCi, or less than 300 mCi if salivary complications are a concern.”

In patients who have intermediate-risk disease, radioiodine may have either an ablative or therapeutic effect. As adjuvant therapy, radioiodine may destroy residual small-volume cancer in patients with nodal or diffuse lung metastases, , for example. As primary therapy, it may be used in patients with RAI-avid disease or metastases.

RAI therapy is recommended for patients with metastases in the lungs, and this should be repeated every 6 to 12 months because the highest rates of complete remission are reported in this patient subgroup. RAI therapy should also be performed for iodine-avid bone metastases, although it is rarely curative for these patients.

According to Grewal, if RAI remnant ablation is performed after total thyroidectomy for low-risk or intermediate-risk thyroid cancer with low-risk features, the recommended dose of I-131 is 30 mCi and is favored over higher-administered activities. As initial adjuvant therapy for microscopic residual disease, administered activities of up to 150 mCi are generally recommended in the absence of known distant metastases, but it is uncertain if higher administration would reduce structural disease recurrence for T3 and N1 disease. Khandani then reviewed the recommended dosing of RAI therapy based on the most recent data (TABLE 2).1

Guiding Principles of RAI Theranostics

After reviewing data related to RAI therapy in differentiated thyroid cancer, Khandani spotlighted the radiotherapeutic agent lutetium Lu-177 dotatate (Lutathera), which was approved for use in patients with somatostatin receptor—positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in January 2018 based on results from the phase III NETTER-1 trial.4He said the protocol for this radiotherapeutic is rigid, and patients receiving this regimen are not followed by a nuclear medicine physician, unlike the traditional scenario for patients receiving RAI.

“I am not sure that we will develop such good handling of these patients compared to RAI in thyroid cancer,” he said. “But with better cooperation with the oncologist, we can look at each patient individually and change the dose accordingly.”


  1. Grewal RK, Khandani AH. Differentiated thyroid cancer management and therapy update. Presented at: Society of Nuclear Medicine and Molecular Imaging 2019 Annual Meeting; June 22-25, 2019; Anaheim, CA. Abstract TS17.
  2. Pontius LN, Oyekunle TO, Thomas SM, et al. Projecting survival in papillary thyroid cancer: a comparison of the seventh and eighth editions of the American Joint Commission on Cancer/Union for International Cancer Control Staging Systems in two contemporary national patient cohorts.Thyroid. 2017;27(11):1408-1416. doi: 10.1089/thy.2017.0306.
  3. Tuttle RM, Sabra MM. Selective use of RAI for ablation and adjuvant therapy after total thyroidectomy for differentiated thyroid cancer: a practical approach to clinical decision making.Oral Oncol. 2013;49(7):676-68 doi: 10.1016/j.oraloncology.2013.03.444.
  4. FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETs. FDA website. Published January 26, 2018. Accessed July 18, 2019.