Clinical Application Study of [123I]Metaiodobenzylguanidine and Somatostatin Receptor-Targeted Imaging in the Diagnosis and Staging of Neuroblastoma (MIBG & SSTR NB)

July 17, 2025 updated by: Nanjing First Hospital, Nanjing Medical University

The goal of this prospective observational study is to evaluate the diagnostic performance of ¹²³I-MIBG SPECT/CT and SSTR PET in Chinese children with suspected or confirmed neuroblastoma (NB). The main questions it aims to answer are:

  • What are the sensitivity and specificity of each modality-alone and combined-for initial staging and for detecting relapse or metastasis?
  • Can SSTR-targeted PET reliably identify MIBG-negative NB lesions and help select candidates for peptide-receptor radionuclide therapy (PRRT)?

Pediatric patients (≤18 years) undergoing routine evaluation for NB will receive both imaging studies; results will be correlated with histopathology, clinical course, and 24-month follow-up.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Neuroblastoma (NB) is the most common extracranial solid tumor in children. More than 50 % of cases occur before the age of two, while diagnoses after 10 years old are rare. NB accounts for approximately 6 - 10 % of pediatric malignancies. Its biological behavior is highly heterogeneous, with diverse molecular features, a high risk of metastasis, and often occult primary sites, making early detection and definitive diagnosis difficult [1-3]. Rapid disease progression further complicates treatment.

In recent years, driven by large international multicenter collaborations, the diagnosis and management of pediatric NB have entered an era of molecular imaging and targeted theranostics. Especially overseas, rapid advances in screening, diagnosis, treatment research, and clinical translation have yielded well-established guidelines and consensus statements, markedly improving the 5-year survival rate [4]. In contrast, research and clinical translation in China lag behind, and understanding of NB biology varies across regions, leading to uneven diagnostic and therapeutic levels without unified protocols. As a result, an increasing number of Chinese patients seek molecular imaging and targeted therapy abroad. Accelerating domestic translation of new NB technologies is thus critical to improving outcomes.

Nuclear medicine imaging (molecular imaging) employs radionuclide-labeled tracers for early lesion detection. For NB, modalities include classic radioiodinated metaiodobenzylguanidine (MIBG) imaging (¹³¹I/¹²³I/¹²⁴I-MIBG, ¹⁸F-MFBG), ¹⁸F-FDG metabolic imaging, somatostatin-receptor (SSTR)-targeted imaging (⁶⁸Ga-DOTA-TATE/TOC/NOC peptides), and ¹⁸F-DOPA imaging. With continual upgrades of SPECT/CT, quantitative SPECT/CT, and PET/CT-MRI, comparative studies on diagnostic accuracy, staging, early detection of relapse/metastasis, radiation safety, and therapy response assessment have flourished. International indications for NB radionuclide imaging include [5-7]: confirmation of suspected NB/pheochromocytoma/ganglioneuroma, disease staging, treatment planning and response evaluation, post-therapy follow-up, and selection for radionuclide therapy.

NB cells overexpress the norepinephrine transporter; hence norepinephrine analogs such as MIBG are ideal imaging (and therapeutic) ligands. Radioiodinated MIBG accumulates in neural-crest-derived tissues and tumors, exhibiting high sensitivity (88-92 %) and specificity (83-92 %) [8]. It distinguishes residual tumor from non-specific findings on anatomic imaging and more accurately evaluates bone marrow metastases than MRI [10, 11]. ¹³¹I-MIBG is widely used therapeutically, and post-therapy ¹³¹I-MIBG scans assess tracer uptake, disease status, and predict response, forming part of theranostic guidelines [8, 9, 12-14]. However, ¹³¹I emits high-energy γ-photons (364 keV) and has a long half-life, resulting in poorer SPECT image quality and lower sensitivity than ¹²³I (159 keV, much shorter half-life). The shorter half-life of ¹²³I permits higher administered activity within the same radiation dose, yielding superior images [15]. Consequently, ¹²³I-MIBG is expected to become the optimal screening tool for selecting patients for ¹³¹I-MIBG therapy. In high-risk NB, ¹²³I-MIBG detects recurrent bone metastases in 94 % of cases versus 43 % for ¹⁸F-FDG PET/CT [9, 10]. MIBG imaging remains the standard for staging and treatment assessment [16-18].

About 10 % of NBs show low or absent MIBG uptake, risking false-negative results. Combining modalities helps overcome this limitation. Somatostatin, a hypothalamic peptide that inhibits pituitary growth hormone and gastrointestinal hormones [19-21], binds receptors found on pancreatic, neuroendocrine, meningeal, and breast tumors [21-24]. High-affinity SSTRs are expressed in 77-89 % of NB cells [25-28]. Numerous ⁶⁸Ga-DOTA peptides target SSTRs, such as ⁶⁸Ga-DOTA-TATE (highest affinity for SSTR2), ⁶⁸Ga-DOTA-TOC (SSTR5), and ⁶⁸Ga-DOTA-NOC (SSTR3 and SSTR5) [29]. Compared with ¹²³/¹³¹I-MIBG, SSTR-PET/CT offers advantages: faster plasma clearance (2 h vs 2 days), same-day injection and imaging, shorter ⁶⁸Ga half-life (68 min vs 13.1 h/8 days), rapid acquisition (20-40 min vs ~1 h), and minimal preparation (no Lugol's solution). One study showed ⁶⁸Ga-DOTA-TOC PET/CT sensitivity of 94.4 %, significantly higher than ¹²³I-MIBG (76.9 %).

Systematic data on MIBG and SSTR imaging in Chinese NB are scarce. Peptide receptor radionuclide therapy (PRRT) with agents like ¹⁷⁷Lu-DOTA-TATE-proven feasible and safe abroad [30, 31]-is attractive, offering outpatient treatment without thyroid blockade, simplifying care for children and families. Small studies have applied PRRT to relapsed pediatric NB [32-35].

Given tumor heterogeneity, different molecular probes deliver complementary diagnostic and therapeutic information. Although combination imaging is well studied internationally, domestic data are lacking. Ethnic and regional factors warrant investigation. This study will employ ¹²³I-MIBG SPECT/CT fusion and SSTR PET/CT or(and) MRI for NB diagnosis, staging, and follow-up, aiming to provide valuable insights for early definitive diagnosis, precise staging, radionuclide-targeted therapy, and response evaluation in Chinese patients. In heterogeneous tumors, multimodal imaging is expected to offer clear advantages for staging, phenotype characterization, prognostication, and treatment planning.

Study Type

Observational

Enrollment (Estimated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • Nanjing First Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Target population

  • Consecutively enrolled neuroblastoma (NB) patients aged 0-18 years, of any sex;
  • Inclusive of all INSS stages Ⅰ-ⅣS and risk groups (low, intermediate, high), covering newly diagnosed, relapsed, and refractory cases;
  • Pathologically confirmed NB, or highly suspected NB based on characteristic imaging plus elevated urinary VMA/HVA, with at least one measurable lesion on routine CT/MRI;
  • Primary and metastatic cases (bone, bone marrow, liver, lymph nodes, etc.) at different treatment stages (before treatment, during treatment, follow-up) are allowed to ensure representativeness in age, sex, histology, stage, and metastatic site distribution.

Description

Inclusion Criteria:

  1. Ages 0-18 years, any sex
  2. Histologically confirmed or clinically highly suspected neuroblastoma with planned imaging assessment
  3. At least one measurable lesion on conventional imaging such as CT or MRI
  4. ECOG performance status 0-2 and an expected survival of ≥3 months
  5. Hematologic, hepatic, and renal function meeting the following criteria: Hb ≥ 90 g/L, ANC ≥ 1.5 × 10⁹/L, platelets ≥ 100 × 10⁹/L, ALT/AST ≤ 2.5 × ULN, Cr ≤ 1.5 × ULN
  6. Informed consent signed by the subject or legal guardian

Exclusion Criteria:

  1. Known history of severe allergy to the radioactive isotope or molecular probe components to be used;
  2. Pregnancy or lactation;
  3. Receipt of high-dose chemotherapy/radiotherapy, radionuclide therapy, or participation in other interventional clinical trials within the past 4 weeks;
  4. Severe or uncontrolled cardiac, pulmonary, hepatic, or renal insufficiency, or active severe infection;
  5. Bone marrow suppression not yet recovered (Hb < 90 g/L, ANC < 1.5 × 10⁹/L, platelets < 100 × 10⁹/L);
  6. Inability to complete imaging examinations such as PET/CT (e.g., severe claustrophobia, inability to lie supine for ≥ 30 min);
  7. Any other situation deemed inappropriate for enrollment by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pediatric Neuroblastoma Imaging Cohort
This cohort includes pediatric patients (≤18 years) with suspected or confirmed neuroblastoma. Interventions include diagnostic imaging with ¹²³I-MIBG SPECT/CT and SSTR PET/CT for staging, therapy planning, and disease monitoring.
Diagnostic test: ¹²³I-MIBG SPECT/CT
Patients take Lugol's iodine 2 days and on the day of injection for thyroid blockade. ¹²³I-MIBG (3-5 MBq/kg; max 370 MBq) is given IV. Whole-body planar imaging is performed 24 h post-injection, then focused SPECT/CT of any suspicious areas with low-dose CT; children are sedated only if motion control is required.
Diagnostic test: SSTR PET
Patients receive an intravenous bolus of 68Ga-DOTA-TATE (1.8-2.2 MBq/kg, max 200 MBq). After a 45-60 min uptake phase, a low-dose whole-body PET/CT or PET/MRI (skull base-mid-thigh) is acquired for ~20 min; MRI or CT provides attenuation correction. Sedation used when required.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SUVmean
Time Frame: baseline and 6 months
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).
baseline and 6 months
SUVmax
Time Frame: Baseline and 6 months
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).
Baseline and 6 months
SUVpeak
Time Frame: baseline and 6 months
SUVpeak is obtained by drawing a fixed-size, 1 cm³ spherical volume of interest centered on the hottest voxel within the tumor on attenuation-corrected PET images; the mean activity concentration inside this sphere is normalized to injected dose per body weight to yield SUVpeak, minimizing noise while reflecting maximal metabolic activity.
baseline and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanjing First Hospital, Nanjing Medical University

Collaborators

Jiangsu Province Hospital of Traditional Chinese Medicine

Investigators

  • Study Chair: Guoqiang Shao, Dr, Nanjing First Hospital, Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2022

Primary Completion (Estimated)

July 10, 2027

Study Completion (Estimated)

July 10, 2027

Study Registration Dates

First Submitted

July 6, 2025

First Submitted That Met QC Criteria

July 6, 2025

First Posted (Actual)

July 15, 2025

Study Record Updates

Last Update Posted (Actual)

July 21, 2025

Last Update Submitted That Met QC Criteria

July 17, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KY20220701-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Within 6 months of the end of the trial, trial data are uploaded to http://www.medresman.org.cn/login.aspx

IPD Sharing Time Frame

Beginning 6 months and ending 3 years after the publication of results

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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