Imaging Techniques for Cushing Syndrome

Recruiting at 1 trial location

Overseen By Lynnette K Nieman, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Disqualifiers: Pregnancy, Severe infection, Cardiovascular, 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

Compensation: Varies

Number of Visits: 6

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve methods for locating the source of hormone overproduction in people with ectopic Cushing syndrome. Traditional imaging methods sometimes fail to detect the small tumors responsible, so the study tests new imaging techniques that focus on body function rather than structure. Participants will undergo special PET scans using new tracers, such as 18F-DOPA and 68Ga-DOTATATE, to determine if these can more accurately identify problem areas. This trial suits those diagnosed with or suspected to have ectopic Cushing syndrome and willing to undergo new imaging procedures. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that these imaging techniques are safe?

Research shows that both 18F-DOPA and 68Ga-DOTATATE are generally safe for use in PET scans. 18F-DOPA, a tracer, has been safely used to image neuroendocrine tumors and Parkinson's disease. Studies have found it helps visualize certain brain tumors without major safety concerns. In contrast, 68Ga-DOTATATE is often used to detect neuroendocrine tumors and has FDA approval for this purpose. Reports confirm its safety for PET scans.

Although this trial is in an early phase, with safety still under close observation, the use of these imaging agents in other conditions supports their safety. Participants might experience minor side effects, but serious issues are rare. Always discuss any concerns with the trial team or a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about imaging techniques using 18F-DOPA and 68Ga-DOTATATE for Cushing Syndrome because these methods improve the visualization of tumors responsible for the condition. Unlike traditional imaging options, these PET-CT scans use specific radiotracers that bind more effectively to the tumor cells, providing clearer and more precise images. This could lead to more accurate diagnosis and better-targeted treatments, potentially improving outcomes for patients with Cushing Syndrome.

What evidence suggests that these imaging techniques are effective for localizing ectopic ACTH production in Cushing syndrome?

Research has shown that 18F-DOPA PET/CT is a promising tool for imaging neuroendocrine tumors, significantly aiding doctors in making better treatment decisions. Similarly, 68Ga-DOTATATE PET/CT effectively detects tumors that other methods might miss. It is particularly useful in identifying ectopic ACTH syndrome, where tumors cause high cortisol levels. Both imaging techniques, studied in this trial, offer detailed insights based on the tumor's activity, not just its size or shape. This precision helps accurately locate the source of hormone production in Cushing syndrome. ^{2 6 7 8 9}

Who Is on the Research Team?

Lynnette K Nieman, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

Adults aged 18-80 with suspected ectopic Cushing syndrome, able to return for follow-up. Excludes pregnant/lactating women, those over 136 kg, under 18 or over 90 years old, severe infections/allergies to somatostatin analogues, certain medication users (affecting CYP3A4), and patients with significant heart, blood, liver or kidney issues.

Inclusion Criteria

I might have Cushing syndrome not caused by a pituitary tumor.

I am willing to go back to NIH for follow-up studies.

Exclusion Criteria

Based on the clinical judgment of the attending physician, other medical problems may prompt exclusion

I am over 90 years old.

I am not on medications that affect CYP3A4 and do not have low potassium levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo various imaging techniques including F-DOPA PET/CT, 68Ga-DOTATATE PET/CT, CT, and MRI to localize the source of ectopic ACTH production

6-12 months

Imaging every 6-12 months until tumor is found

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-DOPA
• 68Ga-DOTATATE
• DOTATATE PET-CT
• F-DOPA PET CT

Trial Overview The trial is testing the effectiveness of PET/CT scans using two substances (68Ga-DOTATATE and F-DOPA) compared to routine MRI in locating the source of ACTH causing ectopic Cushing syndrome. It also evaluates if mifepristone improves PET/CT scan sensitivity.

How Is the Trial Designed?

Group I: Imaging Experimental Treatment 7 Interventions

All subjects will be imaged

Who Is Running the Clinical Trial?

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Lead Sponsor

Trials

2,103

Recruited

2,760,000+

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

In a study involving 15 patients with neuroendocrine tumors (NET), both (68)Ga-DOTA-Tyr3-octreotide PET and (18)F-fluoro-L-dihydroxyphenylalanine PET showed a sensitivity of 64% and a specificity of 100%, indicating their reliability in detecting NET lesions.

(68)Ga-DOTA-TOC PET detected significantly more malignant lesions (208) compared to (18)F-DOPA PET (86) and CT (124), suggesting that (68)Ga-DOTA-TOC PET may be more effective for diagnosis and treatment planning in NET patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of (68)Ga-DOTA-Tyr(3)-octreotide and (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography in neuroendocrine tumor patients. Putzer, D., Gabriel, M., Kendler, D., et al.[2016]

The validation of Ga-68-DOTA-Tyr3-octreotate (DOTATATE) production showed that it meets all European Pharmacopoeia quality control standards, with radiochemical purity consistently above 99% across three production runs.

The successful validation process ensures that Ga-68-DOTATATE is a reliable and safe radiopharmaceutical for neuroendocrine tumor imaging, demonstrating reproducibility in quality and efficacy for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of Quality Control Parameters of Cassette-Based Gallium-68-DOTA-Tyr3-Octreotate Synthesis. Sammartano, A., Migliari, S., Scarlattei, M., et al.[2022]

In a study of 28 patients with ectopic ACTH-secreting tumors (ECS), [68 Ga]-DOTATATE PET/CT successfully identified the suspected primary tumor in 65% of cases, leading to surgical intervention in many patients.

The imaging technique also significantly influenced clinical management, resulting in changes for 64% of patients evaluated during follow-up, highlighting its utility in detecting tumors that conventional imaging might miss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Impact of [68 Ga]-DOTATATE PET/CT for the Diagnosis and Management of Ectopic Adrenocorticotropic Hormone - Secreting Tumours. Wannachalee, T., Turcu, AF., Bancos, I., et al.[2020]

In a study of 30 patients with pheochromocytomas and paragangliomas, (68)Ga-DOTATATE PET/CT demonstrated a high sensitivity of 93% for detecting tumors, making it particularly effective for identifying head and neck paragangliomas, especially in patients with SDHD mutations.

While (68)Ga-DOTATATE PET/CT was superior in detecting head and neck tumors, it was less effective than (18)F-FDOPA PET/CT for pheochromocytomas, indicating that different imaging techniques may be needed based on tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective comparison of (68)Ga-DOTATATE and (18)F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases. Archier, A., Varoquaux, A., Garrigue, P., et al.[2019]

Somatostatin receptor scintigraphy using 111In-DTPA-D-Phe-octreotide or 99mTc-EDDA/HYNIC-TOC shows potential clinical utility in diagnosing pituitary adenomas, indicating that targeted imaging can aid in identifying these tumors.

18F-FDG PET/CT scans, while not typically used for pituitary imaging, can incidentally reveal pituitary adenomas in 60% of cases, particularly in macroadenomas, and may also help detect hypophysitis caused by immunotherapy, highlighting its role in monitoring pituitary health in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pituitary in nuclear medicine imaging. Iglesias, P., Cardona, J., Díez, JJ.[2020]

In a study of 20 patients with suspected pituitary pathology, [68Ga]Ga-DOTA-TATE PET/CT effectively identified recurrent Cushing's disease, showing positive uptake in all seven patients, while it was absent in cases of ectopic ACTH secretion.

The imaging technique also successfully localized ectopic ACTH tumors in six out of eight patients with Cushing's syndrome, demonstrating its utility in cases where traditional imaging methods were inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of [68Ga]Ga-DOTA-TATE PET/CT in diagnosis and management of suspected pituitary tumors. Novruzov, F., Aliyev, A., Wan, MYS., et al.[2021]

In a study analyzing 30 PET/CT scans from 18 patients suspected of having ectopic Cushing's syndrome, the tracers [68Ga]-DOTANOC and [18F]FDOPA demonstrated superior diagnostic capabilities compared to [18F]FDG, with [68Ga]-DOTANOC detecting tumors in all cases it was used.

Notably, [18F]FDOPA was the only tracer that did not produce any false positive results, indicating its potential as a reliable option for diagnosing ectopic Cushing's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome. Zisser, L., Kulterer, OC., Itariu, B., et al.[2021]

Positron emission tomography-computerized tomography (PET-CT) using (68)Ga-DOTATOC is effective for accurately localizing the source of adrenocorticotrophic hormone (ACTH) in patients with ectopic ACTH-induced Cushing's syndrome, which is crucial for surgical management.

This imaging technique allows for better identification of occult tumors that may not be visible through conventional imaging methods, improving the planning for surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

⁶⁸Ga-DOTATOC PET-CT in the localization of source of ectopic ACTH in patients with ectopic ACTH-dependent Cushing's syndrome. Venkitaraman, B., Karunanithi, S., Kumar, A., et al.[2018]

In a study of five patients with malignant phaeochromocytoma, the new PET tracer 68Ga-DOTATATE demonstrated superior imaging capabilities compared to the traditional 123I-MIBG, revealing more lesions and providing better resolution.

For patients showing no or low uptake on 123I-MIBG scans, 68Ga-DOTATATE PET imaging should be considered as the next step for assessing disease activity and guiding therapy, particularly for those eligible for treatment with Y-labelled DOTATATE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-DOTATATE PET in neuroectodermal tumours: first experience. Win, Z., Al-Nahhas, A., Towey, D., et al.[2019]

In a study of 20 patients with extra-adrenal paragangliomas (PGL), (68)Ga-DOTA-TOC PET demonstrated a 100% detection rate for metastatic or multifocal disease, significantly outperforming (18)F-DOPA PET, which had a detection rate of only 56%.

Both imaging techniques were equally effective in detecting nonmetastatic PGL, but (68)Ga-DOTA-TOC PET provided superior diagnostic information, making it a better option for pretherapeutic staging, especially in complex cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma. Kroiss, A., Putzer, D., Frech, A., et al.[2021]

The study found that L-type amino acid transporters (LAT1 and LAT2) are significantly overexpressed in pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC) compared to normal tissues, with LAT1 showing a particularly strong increase in PHEO (15.1-fold).

This overexpression of LAT1 provides a molecular basis for the increased uptake of 18F-FDOPA in these tumors, which can enhance the effectiveness of PET imaging in clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors. Barollo, S., Bertazza, L., Watutantrige-Fernando, S., et al.[2019]

Citations

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Impact of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine PET ... (18)F-DOPA PET/CT changed the intended management of 41% of patients with brain tumors, and intended management changes were implemented in 75% of these.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3644207/

18F-Fluorodihydroxyphenylalanine vs other ... In a study comparing FDOPA PET/CT, PET or CT alone in MTC [16], PET identified all 18 lesions as positive, but was unable to definitively localise 4 lesions (22 ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/49/4/573

6-l-18F-Fluorodihydroxyphenylalanine PET in ... 18 F-DOPA PET is a new diagnostic tool for the imaging of various neuroendocrine tumors. This amino acid tracer is taken up through ubiquitous transmembrane ...

4. ejnmmipharmchem.springeropen.com ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-021-00135-y

GMP production of 6-[18F]Fluoro-l-DOPA for PET/CT ... Data from four years of [18F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/cen.12566

Role of 18 F-FDOPA PET/CT imaging in endocrinology 18 F-FDOPA PET/CT is a very useful test for confirmation of diagnosis, staging at initial presentation, restaging and follow-up of PHEO/PGL.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK23043/

L-3,4-Dihydroxy-6-[18F]fluorophenylalanine - NCBI - NIH 6-[ 18 F]Fluoro-L-DOPA (FDOPA) is a radiolabeled analog of L-DOPA used to evaluate the central dopaminergic function of pre-synaptic neurons using positron ...

7. go.drugbank.com go.drugbank.com/drugs/DB13848

Fluorodopa (18F): Uses, Interactions, Mechanism of Action Fluorodopa F 18 is indicated for use with positron emission tomography (PET) to visualize dopaminergic nerve terminals in the striatum.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17920351/

3,4-dihydroxy-6-[18f]-fluoro-L-phenylalanine Positron ... As with some other amino acids, (18)F-FDOPA has also been effective for visualizing brain tumors, either at time of diagnosis or when monitoring for recurrence, ...

9. imaging-cro.biospective.com imaging-cro.biospective.com/resources/fdopa-parkinsons-disease-clinical-trials

[18F]DOPA PET in Parkinson's Disease Clinical Trials [18F]DOPA PET is used to monitor disease progression & response to therapeutic intervention in Parkinson's disease & movement disorders clinical trials.