Diagnostic Imaging for Pheochromocytoma

Recruiting at 1 trial location

Overseen By Catherine M Gordon, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores better methods to diagnose, locate, and treat pheochromocytomas—tumors in the adrenal glands that can cause high blood pressure and other serious health issues. It includes various tests, such as blood and urine tests, imaging scans like [18F]-6F-DA PET/CT and [18F]-DOPA PET/CT, and genetic testing, to identify these tumors. Participants may undergo surgery if a tumor is detected or receive medical treatment if it is not. Suitable candidates include those with known or suspected pheochromocytomas, based on symptoms or family history. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 prior data suggests that these diagnostic imaging methods are safe for detecting pheochromocytoma?

Research has shown that two imaging methods, [18F]-6F-DA and [18F]-DOPA, are used to identify certain tumors. These methods are under study to aid in detecting pheochromocytomas, which can cause high blood pressure.

Studies have found [18F]-DOPA to be generally safe for PET scans in individuals with these tumors. It is already used for other conditions like neuroendocrine tumors and Parkinson's disease, indicating its safety. No major safety issues have been reported.

Less information is available about [18F]-6F-DA, but it is in an early study phase and is being carefully monitored for safety. This phase assesses the body's reaction to the treatment and observes any side effects.

Overall, both imaging methods appear promising for detecting pheochromocytomas, with no major safety concerns reported so far. Study participants are closely monitored to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]-6F-DA and [18F]-DOPA because these imaging agents offer a new way to diagnose pheochromocytoma and paraganglioma (PHEO/PGL) with precision. Unlike traditional imaging methods like CT or MRI, which rely on structural changes, these agents use PET scans to highlight specific chemical processes in the body, potentially identifying tumors that might otherwise be missed. This approach can lead to earlier detection and better treatment planning, which is why there's a lot of interest in these agents.

What evidence suggests that these diagnostic imaging methods are effective for detecting pheochromocytoma?

This trial will evaluate the effectiveness of two imaging methods for diagnosing pheochromocytomas. Studies have shown that a special type of scan, [18F]-DOPA PET/CT, effectively identifies pheochromocytomas, a type of tumor. This scan can detect tumors that other imaging methods might miss, providing clear images that help doctors locate tumors both inside and outside the adrenal glands. Research also indicates that another scan, [18F]-6F-DA PET/CT, is effective in diagnosing these tumors, especially when they have not spread to other parts of the body. Both imaging methods, tested in this trial, enhance doctors' ability to detect and treat pheochromocytomas early, which is crucial for patient health. ^{1 3 4 6 7}

Who Is on the Research Team?

Catherine M Gordon, M.D.

Principal Investigator

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

Are You a Good Fit for This Trial?

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

Signed informed consent is required

My scans suggest I might have a pheochromocytoma or paraganglioma.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11399174/

Diagnostic performance of [68Ga]DOTATATE PET/CT, [18F ... [68Ga]DOTATATE PET/CT had a superior per-lesion detection rate of 98.7% in the detection of spinal bone metastases associated with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00004847

NCT00004847 | Diagnosis of Pheochromocytoma Patients may undergo 18F-FDOPA, 18F-DA, as well as 68Ga-DOTATATE PET/CT . Each scan takes up to about 2 hours. Genetic testing - A small blood sample is ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7424912/

Preoperative 18F-FDG PET/CT in Pheochromocytomas ... We found 18F-FDG PET/CT detected additional lesions in patients with PC/PGL during routine preoperative imaging that affected the type of surgical approach ...

4. academic.oup.com academic.oup.com/edrv/article/43/2/199/6306512

Personalized Management of Pheochromocytoma and ... For cluster 1A, the most sensitive functional imaging modality is [68Ga]-DOTA-SSA PET/CT, while for cluster 1B and cluster 2 tumors [18F] FDOPA PET/CT is more ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/21/17/3888/117443/Superiority-of-68Ga-DOTATATE-PET-CT-to-Other

DOTATATE PET/CT to Other Functional Imaging Modalities in ... Use of 6-[18F]-fluorodopamine positron emission tomography (PET) as first-line investigation for the diagnosis and localization of non-metastatic and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6827093/

Current Management of Pheochromocytoma/Paraganglioma This review provides a guide for practicing clinicians summarizing current management of PCC/PGL according to tumor size, location, age of first diagnosis, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4668210/

18F-FLT PET/CT in the evaluation of pheochromocytomas ... 18F-FDG PET/CT has been proved to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase ...