Imaging Techniques for Cushing Syndrome

Recruiting at 1 trial location

Overseen By Lynnette K Nieman, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Disqualifiers: Pregnancy, Severe infection, Cardiovascular, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Between 10% and 15% of patients with endogenous hypercortisolism (Cushing syndrome) have ectopic (non-pituitary) production of adrenocorticotropin hormone (ACTH) that causes cortisol excess. In approximately 50% of these patients, the tumoral source of ACTH cannot be found initially despite very detailed and extensive imaging, including studies such as computed tomography, magnetic resonance imaging, and octreotide scan (Octreoscan) using the standard dose of indium- 111 pentetreotide (\[111In-DTPA-D-Phe\]-pentetreotide). The sensitivity and specificity of structurally based imaging studies depends on anatomic alterations and the size of the tumor. In contrast, positron emission tomography (PET) and somatostatin ligand imaging detect pathologic tissue based on physiologic and biochemical processes within the abnormal tissue. This protocol tests the ability of \[18F\]-L-3,4-dihydroxyphenylalanine (18F-DOPA) PET, and the somatostatin imaging analogue, 68Ga-DOTATATE-PET, to localize the source of ectopic ACTH production. ...

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 data supports the effectiveness of the treatment for Cushing Syndrome?

Research shows that [68 Ga]-DOTATATE PET/CT is a high-resolution diagnostic tool effective in imaging neuroendocrine tumors, which can help in localizing ectopic ACTH-secreting tumors causing Cushing syndrome. Additionally, [18F]FDOPA PET/CT has shown high sensitivity and specificity in imaging certain neuroendocrine tumors, which may be relevant for similar conditions. ^{1 2 3 4 5}

Is the imaging technique using 68Ga-DOTATATE and 18F-DOPA safe for humans?

The imaging techniques using 68Ga-DOTATATE and 18F-DOPA have been used in various studies for imaging neuroendocrine tumors and other conditions, and they are generally considered safe for human use. These techniques involve PET/CT scans, which are standard imaging procedures in medical practice. ^{2 3 6 7 8}

How does the imaging treatment for Cushing Syndrome differ from other treatments?

The imaging treatment for Cushing Syndrome using 68Ga-DOTATOC PET-CT is unique because it helps accurately locate the source of excess hormone production, which is often hidden and not visible with regular imaging techniques. This precise localization is crucial for planning effective surgical removal of the tumor causing the condition. ^{3 5 9 10 11}

Research Team

Lynnette K Nieman, MD

Principal Investigator

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

Eligibility Criteria

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 between 18 and 80 years old.

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 an adult.

I am over 90 years old.

Trial Timeline

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

Treatment Details

Interventions

• 18F-DOPA (Radiopharmaceutical)
• 68Ga-DOTATATE (Radiopharmaceutical)
• DOTATATE PET-CT (Radiopharmaceutical)
• F-DOPA PET CT (Radiopharmaceutical)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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 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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome. [2021]

2. Germany 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. [2021]

3. Germany 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. [2019]

4. England 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. [2020]

5. Italy 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. [2016]

6. India pubmed.ncbi.nlm.nih.gov

Validation of Quality Control Parameters of Cassette-Based Gallium-68-DOTA-Tyr3-Octreotate Synthesis. [2022]

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

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors. [2019]

8. England pubmed.ncbi.nlm.nih.gov

The value of [68Ga]Ga-DOTA-TATE PET/CT in diagnosis and management of suspected pituitary tumors. [2021]

9. United States 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. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The pituitary in nuclear medicine imaging. [2020]

11. England pubmed.ncbi.nlm.nih.gov

68Ga-DOTATATE PET in neuroectodermal tumours: first experience. [2019]