[68Ga]Ga-DOTA-TOC positron emission tomography outperforms [18F]FDOPA and [18F]FDG PET in pediatric neuroblastoma imaging: a prospective study

Abstract

Purpose: Neuroblastoma is a heterogeneous pediatric malignancy with variable imaging characteristics. Neuroblastoma tumors express SSTR receptors, but the role of [68Ga]Ga-DOTA-TOC in neuroblastoma remains unclear. This study aimed to compare the diagnostic accuracy of [68Ga]Ga-DOTA-TOC PET against [18F]FDOPA PET and [18F]FDG PET in neuroblastoma.

Methods: Patients with histologically confirmed neuroblastoma were prospectively recruited between September 2021 and September 2024. All participants underwent PET imaging using three radiotracers. Each modality was assessed for lesion detectability. Bone lesions were evaluated using the SIOPEN system. PET findings were interpreted as true lesions following multidisciplinary tumor board discussions and confirmed with follow-up imaging. Detectability across modalities was compared using Cochran’s Q test, while maximal standardized uptake values (SUVmax) were analyzed using repeated measures ANOVA and post hoc pairwise comparisons.

Results: Fifteen patients (mean age 6.1 ± 3.4; 6 females and 9 males) underwent paired PET imaging using three different radiotracers, predominantly stage M (13/15 patients) and high risk (14/15 patients). In patient-based analysis, [18F]FDG PET failed to detect active disease in two patients, resulting in a detection rate of 86.7% (13/15), while [68Ga]Ga-DOTA-TOC and [18F]FDOPA PET successfully identified all patients (15/15, 100%). A total of 203 lesions were identified in the lesion-based analysis. [68Ga]Ga-DOTA-TOC PET demonstrated superior detectability (199/203 lesions, 98.0%), compared to [18F]FDOPA PET (129/203, 63.5%) and [18F]FDG PET (122/203, 60.1%) (p < 0.001). SUVmax was highest for [68Ga]Ga-DOTA-TOC PET (5.5 ± 4.0), followed by [18F]FDG PET (1.8 ± 1.4) and [18F]FDOPA PET (0.6 ± 0.5) (p < 0.001). Organ-based analysis revealed that [68Ga]Ga-DOTA-TOC provides superior detection rates in lymph node (55/57, 96.5%), soft tissue (43/43, 100%), bone and bone marrow (89/89, 100%) metastases. SUVmax was generally higher on [68Ga]Ga-DOTA-TOC PET/CT for both primary lesions and metastases (all p < 0.001), except in the liver. The majority of lesions (170/203, 83.7%) exhibited a Krenning score of 2 or higher.

Conclusion: The enrichment of somatostatin receptors in neuroblastoma makes [68Ga]Ga-DOTA-TOC PET a highly effective detection tool compared to [18F]FDOPA PET and [18F]FDG PET. A multimodal imaging approach can enhance disease evaluation and guide personalized therapeutic strategies, potentially facilitating radioligand therapy.

About this publication.

The Di Bella's Method: Use of Somatostatin/Octreotide analogues and/or derivatives (since 1977), prolactin inhibitors Cabergoline and/or Bromocriptine with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea, Melatonin (since 1974), Retinoids (40mg per day Beta-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate), Vitamin D (together with others chemical compounds) in Neuroblastoma (the dosage and administration schedule must be individualised for each patient):

- Neuroblastoma: Complete objective response to biological treatment;

See also: 

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives since 1977);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

The Di Bella's Method: Use of Melatonin since 1974, Somatostatin/Octreotide analogues and/or derivatives since 1977, prolactin inhibitors Cabergoline and/or Bromocriptine associated with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds: the dosage and administration schedule must be individualised for each patient - in several Oncological Pathologies:

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Disease Control after Androgen Deprivation Therapy Combined with Di Bella Multitherapy;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;

- Excellent result in a Mesothelioma case treated exclusively with Di Bella Method for over 4 years and still treatment with positive results;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years.