I-124 PET/CT Dosimetry for Thyroid Cancer

Overseen By Padmasree Veeraraghavan, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best way to use a special scan called 124 I-PET/CT to measure the necessary amount of radioactive iodine treatment (I-131) for thyroid cancer that has spread. It compares two patient preparation methods: stopping thyroid medication to allow natural hormone levels to rise, and using an injection to stimulate hormones. The study seeks to assess if this scan can better predict the treatment's effectiveness on the cancer. This trial may suit individuals with high-risk thyroid cancer that has spread and who have undergone surgery and previous imaging tests. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

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 prior data suggests that this method is safe for thyroid cancer patients?

Previous studies have shown promising results for Iodine-124 (I-124) PET/CT scans in people with differentiated thyroid cancer. Research indicates that I-124 is well-tolerated in humans, with no serious side effects commonly reported. This imaging technique can detect cancer more accurately than traditional methods.

I-124, a type of radioactive drug used for imaging, remains active in the body for a moderate amount of time, which helps minimize potential risks.

Overall, studies suggest that I-124 PET/CT is generally safe for patients and could offer a better way to monitor thyroid cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the I-124 PET/CT dosimetry technique for thyroid cancer because it offers a more precise way to measure how much radiation therapy (I-131) should be used for each person. Unlike standard treatments that often use a one-size-fits-all approach, this method helps tailor the dose specifically to the patient's needs, potentially improving treatment effectiveness and minimizing side effects. By using the I-124 PET/CT scans, doctors can get a better picture of how the cancer is reacting to treatment, which can lead to more personalized and effective care.

What evidence suggests that this trial's treatments could be effective for thyroid cancer?

Research has shown that I-124 PET/CT scans effectively detect recurring or residual disease in individuals with differentiated thyroid cancer (DTC). Studies indicate that I-124 PET/CT is more sensitive than older imaging methods, detecting issues that other scans might miss. These scans provide clear images and help doctors determine the optimal treatment dose to target cancerous areas while minimizing exposure to healthy tissue. Importantly, I-124 PET/CT can help avoid unnecessary treatments by predicting which patients will benefit most from I-131 therapy. In this trial, participants will undergo I-124 PET/CT scans either after thyroid hormone withdrawal or after preparation with human recombinant TSH. This imaging method is particularly useful for planning treatment, especially when combined with these thyroid-stimulating methods. ^{1 5 6 7 8}

Who Is on the Research Team?

Joanna Klubo-Gwiezdzinska, M.D.

Principal Investigator

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

Are You a Good Fit for This Trial?

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

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.

My treatment plan includes BRAF inhibitors for my BRAF mutant tumor.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• I-124
• I-131
• Thyrogen
• Thyroid hormone withdrawal

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Iodine-131 for:

• Differentiated thyroid cancer
• Hyperthyroidism

Approved in United States as Iodine-131 for:

• Differentiated thyroid cancer
• Hyperthyroidism
• Thyroid nodules

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2292795/

The diagnostic value of 124I-PET in patients with differentiated ... Iodine-124 PET may be able to detect recurrent or residual disease in differentiated thyroid carcinoma (DTC) with a higher sensitivity than the conventional ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03841617?term=peptide

The Use of 124-I-PET/CT Whole Body and Lesional ... 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 ( ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/58/7/1146

Recombinant Human Thyroid-Stimulating Hormone Versus ... The objective of this study was to compare the absorbed dose to the critical organs and tumors determined by 124I PET/CT–based dosimetry for 131 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2211568421000851

PET/CT in the management of differentiated thyroid cancer The role of (124)I-PET in diagnosis and treatment of thyroid carcinoma ... The effectiveness of 124I-PET/CT in patients with differentiated thyroid cancer.

5. miamicancerresearch.org miamicancerresearch.org/images/Publications/Thyroid-MTOCP1-124I_PET-CT_in_Patients_with_Differentiated_Thyroid_Cancer.pdf

124I PET/CT in Patients with Differentiated Thyroid Cancer The objectives of this study were to determine the imaging characteristics and clinical feasibility of 124I positron emission tomography/computed tomography ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06961084

Comparison of I-124 PET/CT for the Diagnosis of Thyroid ... This is a single arm prospective trial that evaluates the ability of Iodine-124 (I-124) to detect metastatic thyroid cancer compared to non-interventional, ...

7. richtlijnendatabase.nl richtlijnendatabase.nl/gerelateerde_documenten/f/17259/124I%20PETCT%20in%20Thyroid%20Cancer.pdf

124I PET/CT in Thyroid Cancer 124I PET (/CT) may be able to detect recurrent or residual disease in DTC with a higher sensitivity than the conventional (diagnostic) 131I scans because of the ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5283715/

I-124 Imaging and Dosimetry - PMC I-124 is a PET radiopharmaceutical with a 4.2-day half life. It offers superior imaging characteristics with enhanced spatial resolution and image sensitivity.