18F-DA PET Scan for Neuroblastoma

Overseen By Barry Shulkin, MD

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Phenylephrine, Pseudoephedrine, Labetalol

Disqualifiers: Pregnancy, Lactation, Anesthesia time, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

20 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 better identify and analyze tumors in patients with neuroblastoma or pheochromocytoma. The current method, which uses a tracer called 123I-mIBG, doesn't always clearly show small areas of the disease. Researchers aim to determine if a different tracer, 18F-DA (18F-Fluorodopamine), is safer and more effective. This trial includes patients with known or suspected neuroblastoma or pheochromocytoma who have had recent positive imaging results. Participants will receive an injection of 18F-DA to compare its effectiveness to the current method. As an Early Phase 1 trial, this research focuses on understanding how the new imaging method works in people, offering participants the chance to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that interfere with the study, such as those containing phenylephrine or pseudoephedrine for 48 hours, and labetalol for 6 weeks before the scan.

What prior data suggests that 18F-DA is safe for pediatric patients with neuroblastoma or pheochromocytoma?

Research has shown that 18F-DA, a type of imaging tracer, is safe for humans. It has been successfully used to study pheochromocytoma, a tumor similar to neuroblastoma. Related studies reported no major safety issues with 18F-DA. Researchers monitored side effects for up to two days after injection and found no significant problems. This suggests that 18F-DA is well-tolerated for PET scans in similar situations. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard imaging methods for neuroblastoma, which typically involve techniques like MRI or CT scans, the 18F-DA PET scan offers a unique approach. This treatment uses a special radioactive tracer, 18F-DA, which is injected into the bloodstream and helps in detecting neuroblastoma cells more precisely. Researchers are excited because this method might provide clearer images of tumor activity, potentially leading to earlier detection and better monitoring of the disease. By targeting specific neuroblastoma cells, 18F-DA PET scans could offer a more accurate assessment, which may improve treatment planning and outcomes for patients.

What evidence suggests that 18F-DA is effective for analyzing neuroblastoma?

Research has shown that a new tracer, 18F-DA (18F-fluorodopamine), which participants in this trial will receive, outperforms the current tracer, 123I-mIBG, for examining certain tumors like pheochromocytoma, which resembles neuroblastoma. This new tracer produces clearer images, aiding doctors in detecting small areas of disease. Studies have confirmed that 18F-DA is safe for use. These findings suggest it could be a superior option for identifying and studying neuroblastoma tumors in patients. Researchers believe this could enhance how doctors diagnose and monitor these tumors. ^{1 2 6 7 8}

Who Is on the Research Team?

Barry L Shulkin, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children over 1 year old with known or suspected neuroblastoma or pheochromocytoma, under a St. Jude physician's care. Participants must not be pregnant, breastfeeding, and should avoid pregnancy within one month after the scan. Those on certain medications may need to stop them before joining.

Inclusion Criteria

I am under the care of a St. Jude Children's Research Hospital doctor.

I am not breastfeeding as I might need to undergo treatments involving radiation.

You have had a positive result on a recent imaging test within the last 4 weeks.

Exclusion Criteria

I have stopped taking medications like phenylephrine and pseudoephedrine for 2 days, and labetalol for 6 weeks.

I am under 3 years old and need anesthesia for more than 3 hours.

Inability or unwillingness of patient, parent, or guardian to consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intravenous injection of 18F-DA followed by PET scanning to evaluate tracer localization

1 day

1 visit (in-person)

Follow-up

Participants are monitored for adverse events and tracer biodistribution

up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• 18F-DA

Trial Overview The study tests if a PET scan using the tracer 18F-DA is safe and more effective than the current standard (123I-mIBG) in detecting small areas of neuroblastoma and pheochromocytoma tumors in about 20 patients at St. Jude.

How Is the Trial Designed?

Group I: Injection of 18F-DA Experimental Treatment 1 Intervention

18F-DA will be injected into a vein in the arm or leg, or via central venous access line.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

Residual (18)F-fluoride in (18)F-FDOPA PET imaging can significantly interfere with the interpretation of neuroblastoma scans, particularly at levels ≥4.0%, leading to false-positive results in areas like the growth plates and pelvis.

By implementing strict quality control measures in the production of (18)F-FDOPA, the incidence of batches with high residual (18)F-fluoride was reduced from 33% to 4%, enhancing the accuracy of neuroblastoma diagnosis and surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of residual (18)F-fluoride in (18)F-FDOPA for the diagnosis of neuroblastoma. Huang, YY., Tzen, KY., Liu, YL., et al.[2016]

In a study of 21 children with advanced neuroblastoma, 18F-DOPA PET/CT demonstrated superior diagnostic accuracy compared to CT/MR, achieving 100% sensitivity and 97.3% accuracy in scan-based analysis.

The lesion-based analysis also favored 18F-DOPA PET/CT, with significantly higher sensitivity (90.6% vs. 47.5%) and positive predictive value (96.9% vs. 69.5%), indicating it is a more reliable imaging method for detecting disease in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-DOPA PET/CT in neuroblastoma: comparison of conventional imaging with CT/MR. Lopci, E., Piccardo, A., Nanni, C., et al.[2016]

The catecholamine analogue [123 I]mIBG has been used for imaging neuroblastoma since 1984, utilizing the noradrenaline transporter (NAT) present in most neuroblastoma cells, indicating its established efficacy in this application.

A new method for producing [18 F]FDA from [18 F]FDOPA shows promise as an alternative PET imaging technique for neuroblastoma, as it allows for rapid conversion and demonstrates effective uptake in neuroblastoma cells, potentially enhancing imaging options for neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast enzymatic synthesis of n.c.a. 6-[18 F]fluorodopamine (FDA) from n.c.a. 6-[18 F]FDOPA and the fate of 6-FDOPA and 6-FDA in neuroblastoma and Caki-1 cells after their uptake. Kuçi, Z., Ehrlichmann, W., Sauer, J., et al.[2020]

18F-DOPA PET/CT is significantly more sensitive than 123I-MIBG whole-body scanning in detecting primary tumors and metastases in children with neuroblastoma, with sensitivities of 94% for primary tumors and 100% for bone or bone-marrow metastases compared to 83% and 92% respectively for 123I-MIBG.

Post-therapy, 18F-DOPA PET/CT also outperformed 123I-MIBG in assessing treatment response, with a notable association between higher whole-body metabolic burden scores and progression-free survival, indicating its potential as a prognostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis, Treatment Response, and Prognosis: The Role of 18F-DOPA PET/CT in Children Affected by Neuroblastoma in Comparison with 123I-mIBG Scan: The First Prospective Study. Piccardo, A., Morana, G., Puntoni, M., et al.[2020]

In a study of 55 children with newly diagnosed neuroblastic tumors, higher metabolic activity (measured by SUVmax and SUVmean) was found in MYCN-amplified tumors and higher International Neuroblastoma Risk Group stages, indicating a correlation between tumor activity and aggressiveness.

While higher SUVmax and SUVmean were associated with worse overall survival, they were not independent predictors when considering other factors like MYCN status and treatment risk, suggesting that these PET metrics should be used alongside other prognostic indicators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of pretreatment 18F-FDG positron emission tomography/computed tomography in pediatric neuroblastoma. Sung, AJ., Weiss, BD., Sharp, SE., et al.[2021]

In a study of 32 pediatric patients with stage 3-4 neuroblastoma, midtreatment imaging using 18F-DOPA and 18F-FDG PET/CT scans revealed that certain metabolic parameters, like interim tumor FDG/FDOPA SUVmax and FDOPA whole-body metabolic burden scores, are significant prognostic factors for overall survival and progression-free survival.

Specifically, an interim FDOPA WBMB score of 21.92 or higher and an interim tumor FDG/FDOPA SUVmax score of 0.57 or higher were associated with poorer outcomes, suggesting these imaging metrics could help predict patient prognosis during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Value of Interim 18F-DOPA and 18F-FDG PET/CT Findings in Stage 3-4 Pediatric Neuroblastoma. Ko, KY., Yen, RF., Ko, CL., et al.[2023]

(18)F-DOPA-PET/CT may provide valuable insights into the response to induction chemotherapy in high-risk neuroblastoma, particularly in cases where traditional (123)I-MIBG scans show discrepancies, such as MIBG-negative primary tumors with MIBG-positive bone marrow metastases.

The study highlights the potential of (18)F-DOPA-PET/CT as a complementary imaging tool in assessing treatment response, although further research is needed to establish its clinical role in pediatric neuroblastoma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(18)F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma. Piccardo, A., Lopci, E., Foppiani, L., et al.[2021]

In a study involving 19 patients with stage 3-4 neuroblastoma, (18)F-Dopa PET/CT demonstrated a significantly higher sensitivity (94%) and accuracy (96%) compared to (123)I-MIBG scintigraphy, which had a sensitivity of 65% and accuracy of 64%.

(18)F-Dopa PET/CT not only detected more neuroblastoma localizations (141 out of 156) but also influenced patient management in 32% of paired scans, suggesting it could be a valuable tool for assessing neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 18F-dopa PET/CT and 123I-MIBG scintigraphy in stage 3 and 4 neuroblastoma: a pilot study. Piccardo, A., Lopci, E., Conte, M., et al.[2021]

The new precursor ALPdopamine™ enables the efficient synthesis of 6-[18 F]Fluorodopamine ([18 F]F-DA) for PET imaging, achieving a production time of 56 to 60 minutes with a yield of 26%, meeting FDA quality control standards for human use.

[18 F]F-DA shows significantly higher accumulation in neuroblastoma cells with high norepinephrine transporter (NET) expression, indicating its potential effectiveness for imaging neuroblastoma tumors in pediatric patients, with a clinical trial already approved for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved, one-pot synthesis of 6-[18 F]fluorodopamine and quality control testing for use in patients with neuroblastoma. Vāvere, AL., Neumann, KD., Butch, ER., et al.[2020]

In a study of 51 high-risk neuroblastoma patients, PET scans were found to be highly effective in detecting tumors, identifying 32.5% of cases that were missed by traditional bone marrow and urine tests.

PET scans outperformed MIBG scans in detecting neuroblastoma in soft tissue and skeletal structures, making it a valuable tool for monitoring disease progression after the primary tumor is removed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extending positron emission tomography scan utility to high-risk neuroblastoma: fluorine-18 fluorodeoxyglucose positron emission tomography as sole imaging modality in follow-up of patients. Kushner, BH., Yeung, HW., Larson, SM., et al.[2017]

In a study of 46 children with neuroblastoma, 18F-DOPA PET/CT was found to detect significantly more lesions than 131I-MIBG, particularly in metastatic skeletal lesions, indicating its potential for better disease evaluation.

Both 131I-MIBG and 18F-DOPA PET/CT can be used interchangeably for staging neuroblastoma, and standardized scoring systems like SIOPEN and Curie can be applied to 18F-DOPA PET/CT to assess disease extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Role of 18F-DOPA PET/CT and 131I-MIBG Scintigraphy in Neuroblastoma and Application of Curie and SIOPEN Scoring Systems in 18F-DOPA PET/CT. Hemrom, A., Arora, G., Damle, NA., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03541720

18F-Fluorodopamine PET Studies of Neuroblastoma and ... Study Overview​​ 18F-DA (18F-fluorodopamine) has been shown to be safe and more effective than 123I-mIBG in analyzing the tumor pheochromocytoma, which is ...

2. stjude.org stjude.org/care-treatment/clinical-trials/flopet-neuroblastoma.html

FLOPET: 18F-DA PET Scans for Neuroblastoma and ... The main goal of this study is to test the safety of 18F-DA in children with neuroblastoma or pheochromocytoma. Researchers also want to learn how 18F-DA moves ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38605509/

Feasibility of 18 F-DOPA and 18 F-FDG PET/CT for guiding ... This study demonstrates the potential utility of 18 F-DOPA and 18 F-FDG PET/CT scans in aiding clinical decision-making for infants with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0969805122020674

Rapid, high-yield enzymatic synthesis of n.c.a. 6-[18F] ... 6-[18F]Fluorodopamine (6-[18F]FDA) proved valuable as a diagnostic tool for neuroendocrine and rare tumors, such as ganglioneuromas and pheochromocytomas, ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03541720/18f-fluorodopamine-pet-studies-of-neuroblastoma-and-pheochromocytoma?dt_type=updated&id=342&slug=neuroblastoma

18F-Fluorodopamine PET Studies of Neuroblastoma and ... ... 18F-DA (18F-fluorodopamine) has been shown to be safe and more effective than 123I-mIBG in analyzing the tumor pheochromocytoma, which is ...

6. clinicaltrial.be clinicaltrial.be/en/details/68495?only_active=0&only_eligible=0&only_recruiting=0&per_page=20

18F-Fluorodopamine PET Studies of Neuroblastoma and ... The adverse events will be recorded and monitored up to two days after the injection of radiotracer 18F-DA. The 95% CI for the adverse event ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39641193/

Safety observations in neuroblastoma patients undergoing ... In this investigation of the potential clinical utility of m FBG PET imaging, no significant adverse safety signals were noted.

8. ancora.ai ancora.ai/de/detailsradiopharm/NCT03541720

18F-Fluorodopamine PET Studies of Neuroblastoma and ... 18F-DA (18F-fluorodopamine) has been shown to be safe and more effective than 123I-mIBG in analyzing the tumor pheochromocytoma, which is closely related to ...