Diagnostic Imaging for Pheochromocytoma

Recruiting at 1 trial location

Overseen By Christina Tatsi, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 1

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

Disqualifiers: Pregnancy, Cardiac dysfunction, Dialysis, others

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

Compensation: Varies

Number of Visits: 1

3000 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

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

What data supports the effectiveness of this treatment for pheochromocytoma?

Research shows that using 18F-DOPA PET/CT is very effective in accurately detecting and locating pheochromocytoma tumors, which is crucial for successful treatment. This combination of imaging techniques offers excellent specificity and sensitivity, making it a valuable tool for diagnosing this condition. ^{1 2 3 4 5}

Is the diagnostic imaging using [18F]-6F-DA and [18F]-DOPA safe for humans?

The research does not provide specific safety data for humans regarding the use of [18F]-6F-DA and [18F]-DOPA in diagnostic imaging for pheochromocytoma. ^{1 2 5 6 7}

How is 18F-FDOPA PET/CT imaging unique for diagnosing pheochromocytoma?

18F-FDOPA PET/CT imaging is unique because it combines two techniques: PET, which uses a special dye to highlight areas of the body, and CT, which provides detailed images of the body's internal structures. This combination allows for more accurate detection and localization of pheochromocytoma tumors compared to using each method alone. ^{1 2 4 8 9}

What is the purpose of this trial?

The goal of this study is to develop better methods of diagnosis, localization, and treatment for pheochromocytomas. These tumors, which usually arise from the adrenal glands, are often difficult to detect with current methods. Pheochromocytomas release chemicals called catecholamines, causing high blood pressure. Undetected, the tumors can lead to severe medical consequences, including stroke, heart attack and sudden death, in situations that would normally pose little or no risk, such as surgery, general anesthesia or childbirth. Patients with pheochromocytoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Study participants will undergo blood, urine, and imaging tests, described below, to detect pheochromocytoma. If a tumor is found, the patient will be offered surgery. If surgery is not feasible (for example, if there are multiple tumors that cannot be removed), evaluations will continue in follow-up visits. If the tumor cannot be found, the patient will be offered medical treatment and efforts to detect the tumor will continue. Main diagnostic and research tests may include the following: 1. Blood tests - mainly measurements of plasma or urine catecholamines and metanephrines as well as methoxytyramine. If necessary the clonidine suppression test can be carried out. 2. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 123I-MIBG scintigraphy and FDG (positron emission tomography) PET/CT. These scans may be done before and/or after surgical removal of pheochromocytoma. 3. Research PET scanning is done using an injection of radioactive compounds. Patients may undergo 18F-FDOPA, 18F-DA, as well as 68Ga-DOTATATE PET/CT . Each scan takes up to about 2 hours. 4. Genetic testing - A small blood sample is collected for DNA analysis and other analyses.

Research Team

Christina Tatsi, M.D.

Principal Investigator

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

Eligibility Criteria

This trial is for adults and children aged 3 years or older with known pheochromocytoma, a tumor that can cause high blood pressure. Participants need to have specific biochemical markers or genetic mutations indicative of the condition, be willing to provide samples, return for follow-up at NIH, and have an outside general practitioner. Pregnant women, those with severe heart issues or kidney dysfunction are excluded.

Inclusion Criteria

Signed informed consent form is required for family members of patients enrolled in this study arm

My scans suggest I might have a pheochromocytoma or paraganglioma.

Signed informed consent is required

Exclusion Criteria

I have severe heart problems.

I am willing to visit the NIH for follow-ups for more than 2 years.

My child cannot understand the study due to mental capacity.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Diagnostic Evaluation

Participants undergo blood, urine, and imaging tests to detect pheochromocytoma. If a tumor is found, surgery is offered.

4-8 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after diagnostic evaluation and potential surgery. Evaluations continue if surgery is not feasible.

12 weeks

Regular follow-up visits (in-person)

Research and Genetic Testing

Participants may undergo genetic testing and research PET scanning to study genotypes and imaging phenotypes.

Ongoing

Treatment Details

Interventions

• [18F]-6F-DA
• [18F]-DOPA

Trial Overview The study aims to improve diagnosis and treatment of pheochromocytomas using various tests including blood/urine analysis for catecholamines/metanephrines, imaging scans like CT/MRI/PET with radioactive compounds ([18F]-6F-DA), ([18F]-DOPA), and genetic testing. Surgery may be offered if tumors are found; otherwise medical management will continue.

Participant Groups

Group I: Adults or children with suspected PHEO/PGL Experimental Treatment 2 Interventions

Patients are adults or children of any age with known, sporadic or familial PHEO/PGL

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+

Findings from Research

In a study involving 14 patients suspected of having pheochromocytomas, (18)F DOPA PET demonstrated a 100% sensitivity in detecting tumors, outperforming MIBG scintigraphy, which had a sensitivity of only 71%.

Both (18)F DOPA PET and MR imaging showed 100% specificity, indicating that (18)F DOPA PET is a highly reliable imaging method for identifying pheochromocytomas and may be a promising option for future clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pheochromocytomas: detection with 18F DOPA whole body PET--initial results.. Hoegerle, S., Nitzsche, E., Altehoefer, C., et al.[2022]

The combination of (18)F-DOPA PET/CT provides a 100% sensitivity and 88% specificity in accurately diagnosing and localizing pheochromocytoma (PHEO) lesions, outperforming either modality alone.

While (18)F-DOPA PET can identify PHEO lesions, it struggles with localization, whereas CT can localize lesions but often fails to confirm their presence; the combined approach resolves these limitations effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma. Luster, M., Karges, W., Zeich, K., et al.[2021]

In a retrospective study of patients with pheochromocytoma, (18)F-DOPA PET/CT demonstrated higher sensitivity (82%) compared to (131)I-MIBG scintigraphy (68%), making it more effective in detecting lesions.

Both imaging techniques showed 100% specificity, but (18)F-DOPA PET/CT was superior in localizing lesions and evaluating paragangliomas, suggesting it may be the preferred method for diagnosis and follow-up in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in evaluating patients with pheochromocytoma. Bandopadhyaya, GP., Kumar, A., Kumari, J.[2019]

In a study of 25 patients with suspected pheochromocytoma, (18)F-FDOPA PET and PET/CT demonstrated high sensitivity (84.6%) and specificity (100%) for accurately detecting and localizing tumors, making it a reliable diagnostic tool.

The study found no significant difference in the maximum standardized uptake value (SUVmax) between benign and malignant tumors, indicating that while (18)F-FDOPA PET is effective for diagnosis, it may not differentiate between tumor types based on uptake levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDOPA PET and PET/CT accurately localize pheochromocytomas. Imani, F., Agopian, VG., Auerbach, MS., et al.[2015]

The study established that 6-(18)F-Fluorodopamine ((18)F-FDA) PET is highly effective in identifying pheochromocytoma (PHEO) in adrenal glands, with all PHEO cases showing significant tracer accumulation.

Cutoff values for standardized uptake values (SUVs) were determined, with a cutoff of 7.3 providing 100% sensitivity and 10.1 providing 100% specificity for distinguishing PHEO-affected adrenal glands from normal ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of standardized uptake values for distinguishing adrenal glands with pheochromocytoma from normal adrenal glands by use of 6-18F-fluorodopamine PET. Timmers, HJ., Carrasquillo, JA., Whatley, M., et al.[2016]

In a study of five patients with metastatic pheochromocytoma, [(123)I]-MIBG scans significantly underestimated the extent of disease compared to CT and MRI, highlighting its limitations in accurately detecting lesions.

In contrast, [18F]-DA scans detected all lesions identified by [(123)I]-MIBG and revealed additional lesions, but still missed some seen on CT and MRI; thus, [18F]-FDG PET is recommended as a supplementary imaging test for better localization of metastatic pheochromocytoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine- and [(123)I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites. Mamede, M., Carrasquillo, JA., Chen, CC., et al.[2019]

In a study using mice, [(18)F]-DOPA was found to be more effective than [(18)F]-DA in detecting metastatic pheochromocytoma, showing better tumor-to-liver ratios and sensitivity for identifying lesions.

MRI outperformed both microCT and PET imaging techniques in detecting all organ tumors, highlighting the importance of imaging method choice in accurately diagnosing pheochromocytoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma. Martiniova, L., Cleary, S., Lai, EW., et al.[2021]

In a study of 38 patients with malignant pheochromocytoma, (18)F-FDG PET/CT demonstrated a higher detection rate of neoplastic tissue (86.8%) compared to (123)I-MIBG SPECT (78.9%), indicating its superior efficacy for restaging this tumor.

(18)F-FDG PET/CT was found to be more accurate than both CT and (123)I-MIBG SPECT for restaging patients with pheochromocytoma, suggesting it should be preferred for monitoring after surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of (18)F-FDG PET/CT, (123)I-MIBG SPECT, and CT in Restaging Patients Affected by Malignant Pheochromocytoma. Cantalamessa, A., Caobelli, F., Paghera, B., et al.[2021]

In a study of 39 patients with confirmed pheochromocytomas (PHEO), the metabolic burden (MB) measured by 18F-FDOPA PET/CT was found to strongly correlate with the urinary excretion of catecholamine metabolites, indicating its potential as a predictive factor for catecholamine secretion.

The research also revealed a novel correlation between the PHEO-to-liver SUVmax ratio and the activity of catecholamine release in PHEO cells, suggesting that increased 18F-FDOPA uptake may be linked to heightened catecholamine exocytosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas. Moog, S., Houy, S., Chevalier, E., et al.[2022]

References

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

Pheochromocytomas: detection with 18F DOPA whole body PET--initial results.. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma. [2021]

3. Greece pubmed.ncbi.nlm.nih.gov

Role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in evaluating patients with pheochromocytoma. [2019]

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

18F-FDOPA PET and PET/CT accurately localize pheochromocytomas. [2015]

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

Usefulness of standardized uptake values for distinguishing adrenal glands with pheochromocytoma from normal adrenal glands by use of 6-18F-fluorodopamine PET. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine- and [(123)I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites. [2019]

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

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Role of (18)F-FDG PET/CT, (123)I-MIBG SPECT, and CT in Restaging Patients Affected by Malignant Pheochromocytoma. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas. [2022]