I-124 PET/CT Dosimetry for Thyroid Cancer

Overseen by Joanna Klubo-Gwiezdzinska, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must be taking: BRAF inhibitors

Disqualifiers: Renal failure, Cardiac failure, Depression, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

Study rationale High risk patients with differentiated thyroid cancer (DTC) require therapy with 131 I under thyroid stimulating hormone (TSH) stimulation. There are two methods of TSH stimulation endogenous by thyroid hormone withdrawal (THW) leading to hypothyroidism and exogenous by injection of human recombinant TSH (rhTSH Thyrogen). The appropriate 131-I activity utilized for treatment is either based on empiric fixed dosage choice or individually determined activity based on 131 I dosimetric calculations. Although dosimetry utilizing radioactive iodine isotope 131 I enables calculation of maximum safe dose, it does not estimate the tumoricidal activity necessary to destroy the metastatic lesions. The alternative radioactive isotope of iodine -124 I, used for positron emission tomography (PET) imaging, might be used for calculation not only the maximum safe131 I dose, but also to predict the absorbed dose in the metastatic lesions. Study objectives The primary objective of this study is to compare the 124 I -PET/CT lesional and whole body dosimetry in each individual patient with metastatic radioiodine (RAI)-avid thyroid cancer under preparation with rhTSH and THW. The secondary objective is to evaluate the predicted by PET/CT lesional uptake with the early response to therapy. Study design This is a phase 2 pilot prospective cohort study comparing the lesional and whole body dosimetry within each patient undergoing exogenous (rhTSH) and endogenous (THW) TSH stimulation and followed for 5 years. Interventions Each study participant will undergo rhTSH and THW-aided 124 I-PET/CT dosimetric evaluations and will be subsequently treated with THW-aided RAI activity based on dosimetric calculations enabling maximum safe dosage. The patients will be followed in 12+/-3 months intervals for 5 years. Sample size and population This pilot study will include 30 patients with high risk differentiated thyroid cancer presenting with distant and/or loco-regional metastases.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients who have undergone therapy with BRAF inhibitors or selumetinib for at least 4 weeks may participate, suggesting that some medications might be allowed. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the treatment I-124 PET/CT Dosimetry for Thyroid Cancer?

Research shows that using I-124 PET/CT can improve the accuracy of measuring how much radioactive iodine is absorbed by thyroid cancer, helping doctors tailor treatment plans more effectively. This method has been shown to better detect cancer spread and recurrence, potentially leading to more successful outcomes in treating thyroid cancer. ^{1 2 3 4 5}

Is I-124 PET/CT dosimetry safe for humans?

Research indicates that while I-124 PET/CT can improve treatment planning for thyroid cancer, there are concerns about the safety of radioactive iodine doses, especially in elderly patients, as they can exceed safe levels without careful dosimetry. ^{1 2 6 7 8}

How is the I-131 treatment for thyroid cancer different from other treatments?

The I-131 treatment for thyroid cancer is unique because it uses radioactive iodine to target and destroy cancer cells in the thyroid, and the use of I-124 PET/CT scans allows for precise measurement of radiation dose to tailor the treatment to each patient, improving accuracy and effectiveness. ^{1 2 3 5 6}

Research Team

Joanna Klubo-Gwiezdzinska, M.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Eligibility Criteria

This trial is for adults over 18 with high-risk differentiated thyroid cancer, who've had a total thyroidectomy and may have distant metastases. They should not be pregnant or lactating, must be able to consent, and cannot have serious conditions like renal failure or non-thyroid cancers. Brain/spine metastasis patients are excluded due to risks from TSH-stimulation.

Inclusion Criteria

I am 18 years old or older.

Your body doesn't have enough iodine, which can be measured by collecting urine for 24 hours.

I have thyroid cancer that doesn't respond to radioactive iodine or needs more treatment.

Exclusion Criteria

Pregnant or lactating women per self report

I have cancer that has spread to my brain or spine.

I do not have severe health issues like kidney failure, heart failure, other cancers, or severe depression.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosimetric Evaluation

Participants undergo rhTSH and THW-aided 124I-PET/CT dosimetric evaluations

9 weeks

Treatment

Participants are treated with THW-aided RAI activity based on dosimetric calculations enabling maximum safe dosage

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up visits every 12±3 months

Treatment Details

Interventions

• I-124 (Radioactive Isotope)
• I-131 (Radioactive Isotope)
• Thyrogen (Hormone Therapy)
• Thyroid hormone withdrawal (Hormone Therapy)

Trial Overview The study tests how well I-124 PET/CT dosimetry can predict the effective dose of I-131 therapy in thyroid cancer under two types of TSH stimulation: Thyrogen injections and hormone withdrawal. It's a phase 2 pilot comparing these methods within each patient over five years.

Participant Groups

Group I: 124I PET/CT scan after thyroid hormone withdrawal Active Control 3 Interventions

124I PET/CT scan after preparation with thyroid hormone withdrawal

Group II: 124I PET/CT scan after rhTSH Active Control 3 Interventions

124I PET/CT scan after preparation with human recombinant TSH

I-131 is already approved in Canada, Japan for the following indications:

Approved in Canada as Iodine-131 for:

• Differentiated thyroid cancer
• Hyperthyroidism

Approved in Japan as Iodine-131 for:

• Differentiated thyroid cancer
• Hyperthyroidism

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

I-124 PET imaging offers improved sensitivity and spatial resolution for diagnosing and treating differentiated thyroid cancer compared to traditional gamma scintigraphy, potentially enhancing the detection of recurrent or metastatic disease.

There is a need for more prospective studies to establish optimal dosimetry protocols for I-124, which will help tailor treatment plans to maximize tumor absorption while minimizing toxicity to healthy organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

I-124 Imaging and Dosimetry. Kuker, R., Sztejnberg, M., Gulec, S.[2022]

Radioiodine therapy using 124I PET/CT scans allows for precise estimation of radiation doses to thyroid cancer lesions, improving treatment planning and individualizing therapeutic 131I activity.

This review highlights the importance of 124I in enhancing the accuracy of dosimetry in thyroid cancer treatment, addressing factors that affect PET image quantification and providing a standardized protocol for lesion dosimetry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of 124I PET/CT lesion dosimetry in differentiated thyroid cancer. Weber, M., Binse, I., Nagarajah, J., et al.[2020]

Radioiodine therapy remains one of the most effective treatments for thyroid cancer, but traditionally relied on imprecise dosimetry methods.

The use of (124)I with PET/CT imaging allows for high-resolution measurement of radioiodine distribution in tumors and normal tissues, enabling personalized dosimetry that can improve treatment outcomes by accounting for individual patient differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer. Sgouros, G., Hobbs, RF., Atkins, FB., et al.[2021]

A treatment using the MEK tyrosine kinase inhibitor selumetinib restored radioactive iodine (RAI) uptake in some patients with iodine-131 refractory thyroid cancer, leading to significant and durable responses.

Using Iodine-124 positron emission tomography allowed for precise measurement of radiation dose on a lesion-by-lesion basis, highlighting its potential as an optimal radiotracer for personalized treatment in well-differentiated thyroid cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redifferentiating Thyroid Cancer: Selumetinib-enhanced Radioiodine Uptake in Thyroid Cancer. Larson, SM., Osborne, JR., Grewal, RK., et al.[2020]

Iodine-124 PET/CT significantly enhances the diagnosis and treatment of thyroid cancer by improving the staging of patients, allowing for better detection of metastatic disease and differentiation between low-risk and high-risk patients.

The technique also offers higher sensitivity and spatial resolution compared to traditional gamma scintigraphy, which aids in detecting recurrent disease and enables accurate radiation dosimetry for personalized radioiodine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of (124)I-PET in diagnosis and treatment of thyroid carcinoma. Lubberink, M., Abdul Fatah, S., Brans, B., et al.[2016]

The study involving 15 patients with differentiated thyroid cancer (DTC) demonstrated that (124)I PET/CT imaging has a high sensitivity of 92.5% for identifying lesions, and it detected 22.5% more RAI-avid lesions compared to traditional (131)I scans.

(124)I PET/CT provides valuable insights into the kinetic profiles of thyroid remnants, salivary glands, and metastatic lesions, which can enhance patient-specific treatment planning and improve the understanding of disease extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(124)I PET/CT in Patients with Differentiated Thyroid Cancer: Clinical and Quantitative Image Analysis. Gulec, SA., Kuker, RA., Goryawala, M., et al.[2018]

A study of 328 patients undergoing dosimetry for RAI therapy revealed that fixed dosing strategies often exceed the maximum tolerable activity (MTA) for many patients, particularly those aged 70 and older, where up to 50% could be at risk with higher doses.

Dosimetry-guided RAI therapy is recommended over fixed-dose strategies, especially for older patients and those with specific metastatic conditions, to ensure safety and avoid exceeding the 200 cGy limit to blood or bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empiric radioactive iodine dosing regimens frequently exceed maximum tolerated activity levels in elderly patients with thyroid cancer. Tuttle, RM., Leboeuf, R., Robbins, RJ., et al.[2007]

In a study of 446 Chinese patients with intermediate- to high-risk papillary thyroid cancer, low-dose radioactive iodine (30 mCi) therapy was found to be as effective as high-dose therapy (>100 mCi) for both ablation success and achieving excellent response rates.

The results indicate that increasing the dose of radioactive iodine does not improve outcomes for patients with specific risk factors, such as BRAFV600E mutations or lymph node metastases, suggesting that low-dose RAI could be a safer and equally effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study. Zhang, Y., Wang, C., Zhang, X., et al.[2019]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

I-124 Imaging and Dosimetry. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

The role of 124I PET/CT lesion dosimetry in differentiated thyroid cancer. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer. [2021]

4. Turkey pubmed.ncbi.nlm.nih.gov

Redifferentiating Thyroid Cancer: Selumetinib-enhanced Radioiodine Uptake in Thyroid Cancer. [2020]

5. Italy pubmed.ncbi.nlm.nih.gov

The role of (124)I-PET in diagnosis and treatment of thyroid carcinoma. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

(124)I PET/CT in Patients with Differentiated Thyroid Cancer: Clinical and Quantitative Image Analysis. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Empiric radioactive iodine dosing regimens frequently exceed maximum tolerated activity levels in elderly patients with thyroid cancer. [2007]

8. United States pubmed.ncbi.nlm.nih.gov

30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study. [2019]