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

Trial Summary

What is the purpose of this trial?

PET (positron emission tomography) scans combined with a radioactive tracer will be used to identify and analyze tumors. Currently, the most common tracer used to analyze neuroblastoma tumors is called 123I-mIBG. However, the picture it provides is not always clear enough to see the very small areas of the disease. 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 neuroblastoma. With this research study, the investigators plan to meet the following goals: * Investigate to see if 18F-DA is safe to administer to pediatric patients with known or suspected neuroblastoma or pheochromocytoma * Examine where in the body 18F-DA goes. * Obtain information comparing 18F-DA to 123I-mIBG to see if 18F-DA could replace 123I-mIBG in the future. About 20 people, with known or suspected neuroblastoma or pheochromocytoma, will take part in this Pilot study at St. Jude.

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 data supports the effectiveness of the treatment 18F-DA PET Scan for Neuroblastoma?

Research shows that 18F-DOPA PET/CT is more effective than the traditional 123I-MIBG scan in detecting neuroblastoma tumors and metastases (spread of cancer) in children, making it a better tool for assessing the disease and treatment response. ^{1 2 3 4 5}

Is 18F-DA PET Scan safe for humans?

The 18F-DA PET Scan has passed all FDA-required quality control tests for human use, indicating it is considered safe for humans. A pediatric neuroblastoma imaging trial using 18F-DA PET has been approved, further supporting its safety profile. ^{1 6 7 8 9}

How does the 18F-DA PET scan treatment differ from other treatments for neuroblastoma?

The 18F-DA PET scan is unique because it uses a compound called 6-[18 F]fluorodopamine, which is taken up by neuroblastoma cells through the norepinephrine transporter, providing high-quality images of the tumors. This method offers improved sensitivity over the standard MIBG imaging, allowing for better detection and assessment of neuroblastoma. ^{1 4 8 10 11}

Research Team

Barry L Shulkin, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

(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]

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]

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]

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]

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 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 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]

References

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

18F-DOPA PET/CT in neuroblastoma: comparison of conventional imaging with CT/MR. [2016]

2. United States 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. [2020]

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

Prognostic Value of Interim 18F-DOPA and 18F-FDG PET/CT Findings in Stage 3-4 Pediatric Neuroblastoma. [2023]

4. United States 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. [2017]

5. Germany pubmed.ncbi.nlm.nih.gov

(18)F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma. [2021]

6. England 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. [2020]

7. Germany 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. [2023]

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

Improved, one-pot synthesis of 6-[18 F]fluorodopamine and quality control testing for use in patients with neuroblastoma. [2020]

9. Japan pubmed.ncbi.nlm.nih.gov

Impact of residual (18)F-fluoride in (18)F-FDOPA for the diagnosis of neuroblastoma. [2016]

10. Germany pubmed.ncbi.nlm.nih.gov

Prognostic significance of pretreatment 18F-FDG positron emission tomography/computed tomography in pediatric neuroblastoma. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

Comparison of 18F-dopa PET/CT and 123I-MIBG scintigraphy in stage 3 and 4 neuroblastoma: a pilot study. [2021]