Clinical Application of Somatostatin Receptor and Norepinephrine Transporter Targeted Imaging for Diagnosis and Staging of Neuroblastoma and Pheochromocytoma/Paraganglioma

NCT07195500 | Recruiting DMC

• 1 other identifier: KY20250819-16
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the diagnostic efficacy of somatostatin receptor and norepinephrine transporter targeted imaging (including 18F-MFBG, 123I-MIBG, 131I-MIBG, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE, 68Ga-DOTA-TOC, and other radiolabeled somatostatin analogues) in the diagnosis and staging of neuroblastoma and pheochromocytoma/paraganglioma patients aged 1-70 years. The main questions it aims to answer are: Can molecular targeted imaging using various norepinephrine transporter tracers (18F-MFBG, 123I/131I-MIBG) and somatostatin receptor tracers (68Ga-DOTA-peptides series) accurately detect primary tumors and metastatic lesions in neuroblastoma/pheochromocytoma patients? What is the comparative diagnostic performance (sensitivity, specificity, accuracy) of different molecular imaging techniques compared to histopathological diagnosis as the gold standard? Researchers will compare the imaging findings from multiple tracer types with surgical pathology results to assess diagnostic accuracy and clinical staging precision. Participants will:

• Undergo screening assessments including medical history, physical examination, and laboratory tests
• Receive intravenous injection of selected tracers (18F-MFBG, 68Ga-DOTA-NOC/TATE, or other appropriate agents) at standardized doses followed by PET-CT/MRI imaging at optimal time points
• Undergo histopathological examination within 2 months post-imaging
• Complete safety follow-up for 6 months to monitor for any adverse reactions to the imaging agents

Conditions

Neuroblastoma; Pheochromocytoma; Paraganglioma

Keywords

neuroblastoma; PET; pheochromocytoma; paraganglioma; somatostatin receptor; norepinephrine transporter

Outcome Measures

Primary Outcomes (4)

• SUVmax

  SUVmax is obtained by outlining a 3-D volume of interest (VOI) around the lesion on attenuation-corrected PET images; the software reports the single voxel with the highest activity concentration, normalized to injected tracer dose divided by the patient's body weight (MBq/kg).

  through study completion, an average of 1 year

• SUVmean

  SUVmean is obtained by outlining a 3-D volume-of-interest around the lesion on attenuation-corrected PET images and averaging all voxel values. Standardized uptake values are calculated as voxel activity concentration (kBq/mL) divided by injected activity per body weight (kBq/g).

  through study completion, an average of 1 year

• Diagnostic Accuracy of SSTR and NET-Targeted Imaging

  Per-patient and per-lesion sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy compared to composite reference standard (histopathology when available and/or multidisciplinary clinical adjudication) Area under the receiver operating characteristic curve (AUC-ROC) for quantitative uptake metrics (SUVmax, SUVmean, target-to-background ratios)

  through study completion, an average of 1 year

• Comparative Diagnostic Performance Between Tracer Classes

  Head-to-head comparison of NET-targeted tracers (18F-MFBG, 123I-MIBG, others) versus SSTR-targeted tracers (68Ga-DOTA-peptides, 64Cu-DOTATATE, 18F-SSTR agents, others) in patients undergoing multi-tracer imaging Within-class comparative performance (e.g., 68Ga-DOTATATE vs 68Ga-DOTATOC vs 68Ga-DOTANOC; 18F-MFBG vs 123I-MIBG)

  through study completion, an average of 1 year

Secondary Outcomes (1)

• Inter-reader Agreement

  through study completion, an average of 1 year

Study Arms (1)

Neuroblastoma and PPGL Patients Undergoing SSTR/NET Imaging

This cohort includes patients with suspected or confirmed neuroblastoma (NB) or pheochromocytoma/paraganglioma (PPGL) undergoing somatostatin receptor (SSTR) and/or norepinephrine transporter (NET)-targeted molecular imaging for diagnostic evaluation and staging. Interventions of interest are diagnostic radiopharmaceutical administrations followed by imaging-there is no therapeutic intent. Participants may receive one or more NET tracers, including 18F-MFBG, 123I-MIBG, 131I-MIBG (legacy diagnostic where appropriate), 18F-LMI1195, and/or SSTR tracers, including 68Ga-DOTATATE, 68Ga-DOTATOC, 68Ga-DOTANOC, 64Cu-DOTATATE, 18F-SiTATE, 18F-AlF-NOTA-octreotide, depending on clinical indication and site availability. Imaging is performed on PET/CT or PET/MRI for PET tracers and SPECT/CT for SPECT tracers using harmonized acquisition and reconstruction parameters. When clinically justified

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This single-center cohort comprises pediatric and adult patients with suspected or confirmed neuroblastoma (NB) or pheochromocytoma/paraganglioma (PPGL) who are referred for somatostatin receptor (SSTR) and/or norepinephrine transporter (NET)-targeted molecular imaging as part of diagnostic evaluation, staging, restaging, suspected recurrence assessment, response evaluation, or treatment planning (e.g., selection for peptide receptor radionuclide therapy or 131I-MIBG therapy). Participants are enrolled primarily from oncology, endocrinology, and nuclear medicine clinics of a tertiary academic medical center, with referrals from affiliated hospitals; most imaging is performed in the outpatient setting, with inpatient cases included when clinically indicated. Both sexes and all racial/ethnic groups are eligible, reflecting the catchment population. The study population includes a prespecified subset undergoing multi-tracer imaging when clinically justified and feasible, and a PET/MRI su

You may qualify if:

• Age: ≥6 months (pediatric and adult).
• Suspected or confirmed diagnosis of neuroblastoma (NB) or pheochromocytoma/paraganglioma (PPGL).
• Clinical indication for SSTR and/or NET-targeted molecular imaging for initial staging, restaging, suspected recurrence, response assessment, or treatment planning.
• Ability to undergo PET/CT or PET/MRI and/or SPECT/CT per protocol; for the PET/MRI subset, no MRI contraindications.
• Provision of written informed consent/assent per local regulations.
• Women of childbearing potential: negative pregnancy test within 72 hours prior to tracer administration and agreement to use effective contraception during the imaging window.
• For the multi-tracer subset (if applicable): willingness to undergo two imaging studies within a predefined window (e.g., ≤28 days) without intervening antitumor therapy.

You may not qualify if:

• Pregnant or breastfeeding; breastfeeding participants unwilling to follow tracer-specific lactation interruption guidance per institutional policy.
• Any condition that, in the investigator's judgment, precludes safe imaging or protocol compliance (e.g., uncontrolled cardiorespiratory disease, severe claustrophobia not amenable to sedation/anxiolysis).
• Known hypersensitivity to study radiopharmaceuticals or their excipients.
• Use of interfering medications without feasible washout:
• NET imaging: drugs that affect catecholamine transport/storage (e.g., labetalol, tricyclic antidepressants, certain sympathomimetics) per site SOPs.
• SSTR imaging: long-acting somatostatin analogues within \~3-4 weeks or short-acting within \~24-48 hours, unless clinically unavoidable.
• Prior therapeutic or high-dose 131I-MIBG within a period that would confound diagnostic imaging or dosimetry (e.g., within 6 months), at the investigator's discretion.
• Contraindications to required modality-specific procedures (e.g., MRI-incompatible implants for PET/MRI; iodinated/gadolinium contrast contraindication only if contrast is mandated and no alternative pathway is acceptable).
• Inability to lie still for the required acquisition time and sedation not feasible per institutional policy.
• Concurrent participation in an interventional study or receipt of anticancer therapy that would confound imaging interpretation within the imaging window; for multi-tracer comparisons, any interval systemic therapy between scans.

Sponsors & Collaborators

• Nanjing First Hospital, Nanjing Medical University: lead

Study Sites (1)

Nanjing First Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Related Publications (10)

• Gulaldi NCM, Gulleroglu NB, Cakmakci S, Gortan FA, Sari N. Dilemma on Pancreatic Uncinate Process Uptake on Ga68-DOTA Peptide PET/CT in Pediatric Neuroblastoma: Physiologic or Metastases? Curr Radiopharm. 2025;18(4):333-339. doi: 10.2174/0118744710226018250206105536.

  PMID: 39966364 BACKGROUND

• Liu CJ, Ko KY, Lu MY, Hung WT, Chou SW, Du CJ, Chang HH, Hsu WM, Yang YL, Chien YT, Peng SS, Cheng MF. [68Ga]Ga-DOTA-TOC positron emission tomography outperforms [18F]FDOPA and [18F]FDG PET in pediatric neuroblastoma imaging: a prospective study. Eur J Nucl Med Mol Imaging. 2025 Dec;53(1):192-202. doi: 10.1007/s00259-025-07399-5. Epub 2025 Jun 13.

  PMID: 40512254 BACKGROUND

• Lu Z, Sun Y, Zuo D, Li P, Sun X. Radiation Exposure to Patients and Others During Therapy for Pediatric Neuroblastoma With Lu-177-DOTATATE. Clin Nucl Med. 2025 Jun 1;50(6):480-485. doi: 10.1097/RLU.0000000000005763. Epub 2025 Feb 25.

  PMID: 39992800 BACKGROUND

• Sharp SE, Trout AT, Weiss BD, Gelfand MJ. MIBG in Neuroblastoma Diagnostic Imaging and Therapy. Radiographics. 2016 Jan-Feb;36(1):258-78. doi: 10.1148/rg.2016150099.

  PMID: 26761540 BACKGROUND

• Vik TA, Pfluger T, Kadota R, Castel V, Tulchinsky M, Farto JC, Heiba S, Serafini A, Tumeh S, Khutoryansky N, Jacobson AF. (123)I-mIBG scintigraphy in patients with known or suspected neuroblastoma: Results from a prospective multicenter trial. Pediatr Blood Cancer. 2009 Jul;52(7):784-90. doi: 10.1002/pbc.21932.

  PMID: 19185008 BACKGROUND

• Giammarile F, Chiti A, Lassmann M, Brans B, Flux G; EANM. EANM procedure guidelines for 131I-meta-iodobenzylguanidine (131I-mIBG) therapy. Eur J Nucl Med Mol Imaging. 2008 May;35(5):1039-47. doi: 10.1007/s00259-008-0715-3.

  PMID: 18274745 BACKGROUND

• Shulkin BL, Shapiro B. Current concepts on the diagnostic use of MIBG in children. J Nucl Med. 1998 Apr;39(4):679-88.

  PMID: 9544682 BACKGROUND

• Leung A, Shapiro B, Hattner R, Kim E, de Kraker J, Ghazzar N, Hartmann O, Hoefnagel CA, Jamadar DA, Kloos R, Lizotte P, Lumbroso J, Rufini V, Shulkin BL, Sisson JC, Thein A, Troncone L. Specificity of radioiodinated MIBG for neural crest tumors in childhood. J Nucl Med. 1997 Sep;38(9):1352-7.

  PMID: 9293786 BACKGROUND

• Bombardieri E, Giammarile F, Aktolun C, Baum RP, Bischof Delaloye A, Maffioli L, Moncayo R, Mortelmans L, Pepe G, Reske SN, Castellani MR, Chiti A; European Association for Nuclear Medicine. 131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2010 Dec;37(12):2436-46. doi: 10.1007/s00259-010-1545-7.

  PMID: 20644928 BACKGROUND

• Sharp SE, Shulkin BL, Gelfand MJ, Salisbury S, Furman WL. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med. 2009 Aug;50(8):1237-43. doi: 10.2967/jnumed.108.060467. Epub 2009 Jul 17.

  PMID: 19617326 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood: serum and plasma aliquots collected at imaging time points and/or routine safety labs; selected leftover whole blood in EDTA tubes may be retained for assay validation.

MeSH Terms

Conditions

Neuroblastoma; Pheochromocytoma; Paraganglioma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroendocrine Tumors

Study Officials

• Guoqiang Shao, Dr

  Nanjing First Hospital, Nanjing Medical University

  STUDY DIRECTOR

Central Study Contacts

Guoqiang Shao, Dr

CONTACT

+86 153 6615 5689; guoqiangshao@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2025
• First Posted: September 26, 2025
• Study Start: December 25, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: September 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Beginning 6 months and ending 3 years after the publication of results
• Access Criteria: Qualified academic investigators with an IRB-approved proposal may request access to de-identified individual participant data (IPD), the full study protocol, blank case report forms, and the English/Chinese informed-consent templates. Requests should be emailed to the corresponding author; after signing a data-sharing agreement, files will be shared through a secure, password-protected institutional repository within 30 days.

Locations

CN (1)