Nuclear Imaging for Primary Aldosteronism

Overseen By Alexander Leung, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: Chronic corticosteroids

Disqualifiers: Chronic kidney disease, Severe hypertension, Severe diabetes, Hypercortisolism, 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: 1

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to diagnose Primary Aldosteronism, a condition that can cause high blood pressure. Researchers aim to determine if a special tracer, [18-F]CETO (also known as para-chloro-2-[18F]fluoroethyl etomidate or CETO), used with PET and CT scans, can identify whether one or both adrenal glands are affected. This method could be more accurate than the current standard test. Individuals with high blood pressure and specific hormone levels might be suitable candidates, especially if scans show an adrenal gland issue. 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 advancements in diagnostic accuracy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are using chronic corticosteroids, you may be excluded from participating.

What prior data suggests that this radiopharmaceutical tracer is safe for use in nuclear imaging?

Research shows that [18-F]CETO is a safe choice for PET scans of the adrenal glands. Earlier studies found no negative reactions, and it did not affect adrenal function. Patients experienced no side effects from the treatment. The evidence suggests that [18-F]CETO is well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of [18-F]CETO for primary aldosteronism because it offers a new way to diagnose this condition more accurately. Unlike standard diagnostic methods that rely on hormone tests and imaging to spot abnormalities in the adrenal glands, [18-F]CETO uses a radioactive tracer in conjunction with PET/CT scans to provide more precise imaging. This could lead to better-targeted treatments, as doctors can identify the exact sources of hormone overproduction. By improving diagnosis, this approach has the potential to enhance the overall management and outcomes for patients with primary aldosteronism.

What evidence suggests that this novel radiopharmaceutical tracer is effective for subtyping Primary Aldosteronism?

Research has shown that [18-F]CETO, which participants in this trial will receive, is a promising tool for imaging primary aldosteronism, a condition affecting hormone production in the adrenal glands. Studies have found that [18-F]CETO is safe for use in PET scans, with no harmful side effects reported. The tracer spreads well throughout the body, effectively imaging the adrenal glands. Its ability to show tracer uptake can help determine if one or both adrenal glands are affected. This information is crucial for deciding the best treatment for patients. ^{2 3 4 5 6}

Who Is on the Research Team?

Alexander Leung, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for individuals with Primary Aldosteronism or Conn Syndrome, who have high blood pressure and an elevated adrenal renin ratio. They may also have low potassium levels and a visible adrenal nodule on imaging. It's not for those with severe kidney disease, uncontrolled high blood pressure or diabetes, certain adrenal gland disorders, liver anatomical diseases, pregnant or lactating women, people with pheochromocytoma, allergies to IV contrast, bleeding disorders, or those on long-term steroids.

Inclusion Criteria

You have high levels of a hormone called renin in your adrenal glands.

I have low potassium levels and/or a significant adrenal gland nodule.

I have high blood pressure.

Exclusion Criteria

My kidney function is low (eGFR <40).

I am allergic to IV contrast, have a bleeding disorder, or take steroids regularly.

I do not have uncontrolled high blood pressure, severe diabetes, abnormal cortisol levels, or liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the [18-F] CETO radiopharmaceutical tracer followed by a PET/CT scan to subtype unilateral vs. bilateral forms of Primary Aldosteronism

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the PET/CT scan

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18-F]CETO

Trial Overview [18-F]CETO is being tested in this study using PET/CT scans to differentiate between unilateral and bilateral forms of Primary Aldosteronism. The accuracy of CETO will be compared against Adrenal Vein Sampling (AVS), which is the current gold standard method.

How Is the Trial Designed?

Group I: CETO Experimental Treatment 1 Intervention

The consented participants will receive the \[18-F\] CETO through the IV and a PET/CT scan afterwards.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

In a study involving 25 patients, parametric maps derived from 11C-metomidate PET imaging showed a strong correlation (r2 = 0.96) with regional uptake rates, allowing for effective differentiation between active unilateral adenomas and bilateral hyperplasia, which was not possible with standard uptake ratios.

The use of the parametric metric Ki(mVOX) provided better diagnostic accuracy than SUVmax, successfully identifying three false-negative cases that traditional SUV analysis missed, highlighting its potential as a valuable tool in clinical diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parametric mapping for 11C-metomidate PET-computed tomography imaging in the study of primary aldosteronism. O' Doherty, J., O' Doherty, S., Robins, EG., et al.[2023]

In a study of 17 patients with primary aldosteronism (PA), 11 C-metomidate (MTO) PET imaging showed different uptake patterns based on adrenal CT findings, indicating its potential as a useful imaging biomarker for predicting treatment outcomes.

Patients who responded to medical treatment had significantly lower tracer uptake in MTO PET, suggesting that MTO PET can help identify which patients are likely to benefit from treatment, although further validation in larger studies is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Treatment Response in Primary Aldosteronism Using 11 C-Metomidate Positron Emission Tomography. Lu, CC., Chen, CJ., Peng, KY., et al.[2022]

MTO-PET is highly effective in detecting small adrenocortical adenomas in patients with primary aldosteronism (PA), as all tumors were successfully identified in the study of 13 patients.

Dexamethasone suppression treatment did not significantly enhance the detection of small adenomas by improving the tumor-to-normal adrenal ratio, indicating that while MTO-PET is sensitive, the suppression treatment may not provide additional benefits for tumor differentiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism. Hennings, J., Sundin, A., Hägg, A., et al.[2021]

The new radiotracer [18F]FAMTO was successfully synthesized and showed high selectivity for aldosterone-producing enzymes in adrenal glands, indicating its potential for diagnosing primary aldosteronism.

In vivo studies demonstrated that [18F]FAMTO accumulates rapidly in adrenal glands, with minimal uptake in other organs, suggesting it could be an effective tool for identifying adrenal lesions in patients with hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of [18F]FAMTO: A novel fluorine-18 labelled positron emission tomography (PET) radiotracer for imaging CYP11B1 and CYP11B2 enzymes in adrenal glands. Bongarzone, S., Basagni, F., Sementa, T., et al.[2022]

The new PET tracer [18F]CETO shows high specificity for the adrenal cortex and demonstrates better binding properties compared to the existing tracer [11C]MTO, with a significantly lower non-specific binding in the liver.

In vitro and in vivo studies indicate that [18F]CETO could be a promising option for imaging adrenocortical diseases, warranting further evaluation in human subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Para-chloro-2-[18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging. Silins, I., Sundin, A., Nordeman, P., et al.[2023]

A new PET imaging method using the tracer [68Ga]Ga-PentixaFor shows promise for accurately diagnosing primary aldosteronism (PA) by distinguishing between aldosterone-producing adenomas and bilateral adrenal hyperplasia, potentially offering a safer and cheaper alternative to the invasive adrenal vein sampling (AVS).

The proposed study will assess the accuracy of [68Ga]Ga-PentixaFor PET/CT compared to AVS in a two-step randomized controlled trial, aiming to improve diagnostic outcomes and reduce the need for more complex procedures in patients with PA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS). Chaman Baz, AH., van de Wiel, E., Groenewoud, H., et al.[2022]

The new tracer [18F]CETO shows high uptake in adrenal glands and low uptake in the liver, making it a promising option for adrenal imaging in patients with adrenal tumors.

In a study involving 15 patients and 5 healthy volunteers, the uptake of [18F]CETO correlated well with adrenal blood flow, indicating its potential effectiveness in assessing adrenal function and pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human evaluation of [18F]CETO: a novel tracer for adrenocortical tumours. Silins, I., Sundin, A., Lubberink, M., et al.[2023]

Citations

1. jnm.snmjournals.org jnm.snmjournals.org/content/66/3/434

A Phase I/IIa Clinical Trial to Evaluate Safety and Adrenal ... [ 18 F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11109037/

a PET tracer for adrenocortical imaging - PMC [ 18 F]CETO has a favourable biodistribution in humans for adrenal imaging. The effective dose for a typical clinical PET examination with 200 MBq [ 18 F]CETO ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06616142

Subtyping Primary Aldosteronism With Para-chloro-2-[18F ... The goal of this clinical trial is to investigate the uptake characteristics of [18F]CETO in adrenal tissue in patients with two different subtypes of ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39884776/

A Phase I/IIa Clinical Trial to Evaluate Safety and Adrenal ... [ 18 F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05472493/nuclear-imaging-for-subtype-diagnosis-of-primary-aldosteronism

Nuclear Imaging for Subtype Diagnosis of Primary ... This study is to evaluate the accuracy of a novel radiopharmaceutical tracer, para-chloro-2-[18F]fluoroethyl etomidate (CETO), ...

6. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/fluorine-f-18-para-chloro-2-fluoroethyl-etomidate

Definition of fluorine F 18 para-chloro-2-fluoroethyl-etomidate A radioconjugate composed of para-chloro-2-fluoroethyletomidate (CETO) conjugated to the radioisotope fluorine F 18 (18F), with potential application in ...