gallium-ga-68-dotatate and Neuroblastoma

Topics: Child; Contrast Media; Humans; Multimodal Imaging; Neuroblastoma; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity

Childhood neuroblastoma is a heterogenous disease with varied clinical presentation and biology requiring different approaches to investigation and management. Metaiodobenzylguanidine (MIBG) is an essential component of metastatic staging for neuroblastoma and has been used as a treatment strategy for relapsed and refractory neuroblastoma. However, as 10% of children with neuroblastoma will have 123I-MIBG non-avid imaging and up to 60% with relapsed and refractory neuroblastoma will require further treatment with 131I-MIBG, alternative radioisotopes have been investigated for imaging and treatment. Neuroblastoma tumors express mostly somatostatin receptor- 2 (SSTR2) that can be targeted by somatostatin analogues including DOTA-conjugated peptides e.g. DOTATATE, DOTATOC.. This review summarizes the rationale, utility and experience of DOTA-conjugated peptides in imaging and treatment of childhood neuroblastoma.. Radiolabeled DOTA-peptides are used routinely in adults to image neuroendocrine tumors and have potential to be used to image and treat neuroblastoma. 68Ga-DOTATATE PET/CT has been shown to have better sensitivity, quicker clearance and administration times, reduced radiation exposure and limited toxicity compared to 123I-MIBG. Therapeutic studies of peptide receptor radionuclides e.g. 177Lu-DOTATATE in patients with relapsed neuroblastoma have used 68Ga- DOTATATE PET/CT to determine eligibility for therapy. Further studies would need to investigate appropriate indications, timings, scoring and clinical significance of radiolabeled DOTA-peptide conjugated PET/CT imaging in childhood neuroblastoma.

Topics: 3-Iodobenzylguanidine; Fluorodeoxyglucose F18; Humans; Neoplasm Staging; Neuroblastoma; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography

In treatment of metastatic neuroblastoma, the central nervous system seems to act as a sanctuary leading to often unexpected relapse of disease. We present a case of neuroblastoma treated with chemotherapy and autologous stem cell transplantation only to relapse in central nervous system with meningeal metastases visualized on 68Ga-DOTATOC imaging.

Topics: Aged; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Meningeal Neoplasms; Middle Aged; Neuroblastoma; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Recurrence; Transplantation, Autologous

Recent evidence has demonstrated high expression of somatostatin receptors in neuroblastoma (NB) cells. Because of this, we endeavored to evaluate the diagnostic performance and clinical efficacy of 68Ga-DOTATATE PET/CT and peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE combined with chemotherapy in pediatric NB patients.. In total, 14 pediatric patients with histopathologically confirmed NB underwent 68Ga-DOTATATE PET/CT. Among them, the patients who were refractory or relapsed after therapy with 131I-MIBG and had intensive uptake of 68Ga-DOTATATE were referred for PRRT using 177Lu-DOTATATE. Treatment response based on follow-up imaging was classified into complete response, partial response, stable disease, and progressive disease. After each cycle of PRRT, laboratory tests were performed for evaluation of hematological, renal, and hepatic toxicities. The CTCAE (Common Terminology Criteria for Adverse Events; version 4.03) was used for grading adverse event. Curie score and International Society of Pediatric Oncology Europe Neuroblastoma score were used for semiquantitative analysis of scans of patients who underwent PRRT. In addition, overall survival was calculated as the time interval between the date of the first cycle and the end of follow-up or death.. Overall, 14 refractory NB children including 7 boys and 7 girls with a median age of 5.5 years (ranged from 4 to 9) underwent 68Ga-DOTATATE PET/CT. PET/CT was positive in 10/14 patients (71.4%), and the median number of detected lesions in positive patients was 2 (range, 1-13). Of 14 patients, 5 patients underwent PRRT, including 3 boys and 2 girls. A total of 19 PRRT cycles and 66.4 GBq 177Lu-DOTATATE were given. Among these 5 patients, 2 showed an initial complete response, which relapsed a few months later, 1 showed a partial response, and 2 showed progressive disease. According to the Kaplan-Meier test, the overall survival was estimated at 14.5 months (95% confidence interval, 8.9-20.1). In evaluation of PRRT-related toxicity according to the CTCAE, 4 patients showed grade 1, and 1 showed grade 2 leukopenia. Two patients showed grade 1, and 2 others showed grade 2 anemia. Two patients showed grade 1, and 3 patients showed grade 2 thrombocytopenia. Serum creatinine in 1 patient increased to grade 1.. Combination of 177Lu-DOTATATE with chemotherapeutic agents might achieve worthwhile responses with low toxicity, encouraging survival in NB patients who have relapsed or are refractory to conventional therapy, including 131I-MIBG therapy. Imaging with 68Ga-DOTATATE PET/CT in such patients has a relatively high detection efficacy, demonstrating its potential use as an alternative imaging tool to conventional modalities such as 123I/131I-MIBG. However, further well-designed trials are highly warranted.

Topics: Child; Child, Preschool; Combined Modality Therapy; Coordination Complexes; Feasibility Studies; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Neuroblastoma; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Receptors, Peptide; Receptors, Somatostatin; Recurrence; Treatment Failure

A girl diagnosed with neuroblastoma at 33 months underwent I-MIBG scan after surgery and chemoradiotherapy. Although MIBG scan showed complete response, the bone marrow biopsy showed refractory disease. Therefore, she underwent Ga-DOTATATE PET/CT, which revealed bone marrow involvement and Ga-DOTATATE-avid brain metastasis. Rare physiological pineal gland uptake was also depicted. Ga-DOTATATE PET/CT showed active progressive disease earlier, before it was detectable with MIBG scan. For patients with MIBG-negative relapsed/refractory disease, Ga-DOTATATE may have an important role in restaging, detecting unsuspected metastasis, therapy planning.

Topics: Brain Neoplasms; Child, Preschool; Female; Humans; Neuroblastoma; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals

A 22-month-old boy diagnosed with neuroblastoma was evaluated by bone scintigraphy and I-metaiodobenzylguanidine scintigraphy, and no metastases to skeletal system was detected. However, plain radiograph and MRI revealed suspected metastatic lesions. The patient was therefore evaluated by Ga-DOTA-TATE PET/CT, and Ga-DOTA-TATE uptake was observed in multiple bone and bone marrow areas, which were consistent with metastases. Biopsy was taken from the right iliac bone, and the pathological examination of the biopsy specimen was coherent with neuroblastoma invasion.

Topics: Brain Neoplasms; Humans; Infant; Male; Neuroblastoma; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals

Pediatric patients with refractory neuroblastoma have limited therapeutic options. Neuroblastoma may express somatostatin receptors (SSTRs) allowing imaging with 68Ga-DOTA-Octreotate (GaTATE) positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT). We reviewed our experience with this theranostic combination.. GaTATE studies (8 patients; 2 to 9 years old) were reviewed and compared with 123I-MIBG or posttreatment 131I-MIBG studies. Immunohistochemistry (IHC) for SSTR subtype 2 was performed in 5 patients. Four patients received PRRT.. GaTATE PET showed additional disease in 38% (3/8 patients), and upstaged 1 patient by detecting marrow involvement. IHC detected SSTR 2 in all patients assessed. Six patients were deemed suitable for PRRT on imaging. Four patients received 17 cycles of palliative PRRT (10 111In-DOTATATE; 5 177Lu-DOTATATE; 1 combined 111In and 177Lu-DOTATATE; 1 combined 177Lu and 90Y-DOTATATE) with no significant toxicity attributed to PRRT. All had objective responses. Two survivors are now 40 and 56 months from PRRT commencement.. GaTATE PET was positive in a high proportion of patients with refractory neuroblastoma, correlating with SSTR 2 on IHC, with additional disease identified compared with MIBG imaging. PRRT seems safe, feasible, with responses observed in patients with progression despite multimodality treatment. These data support ongoing clinical trials in such patients.

Topics: 3-Iodobenzylguanidine; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Male; Multimodal Imaging; Neuroblastoma; Octreotide; Organometallic Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, Somatostatin; Retrospective Studies; Tomography, X-Ray Computed

(68)Ga-DOTATATE PET-CT is widely used for the evaluation of neuroendocrine tumours. Knowledge of the physiological distribution of the radiotracer is of critical importance in characterizing focal areas of uptake. In this case series, we report three paediatric cases (average age 4.7 years ± 0.6 SD) with diagnosed advanced stage IV Neuroblastoma. Two had (68)Ga-DOTATATE PET-CT scans and one underwent (68)Ga-DOTATATE PET-MRI scan to assess for suitability of molecular therapy. Focal increased tracer uptake in the pineal gland was noted in all cases with no morphological abnormality on the corresponding CT and MRI scans. The uptake within the gland was thought to be a physiological variant rather than metastases owing to the heterogeneity of somatostatin receptors expression. The pineal gland has been reported to express somatostatin receptors. The physiological distribution of (68)Ga-DOTATATE uptake in the pineal gland is not routinely seen. Furthermore, the possibility of pineal meningioma is very unlikely as pineal meningiomas are very rare and there was no convincing morphological evidence of meningiomas on CT/MRI scan.

Topics: Brain Neoplasms; Child, Preschool; Female; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Neoplasm Staging; Neuroblastoma; Organometallic Compounds; Pineal Gland; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed