177Lu-DOTATATE radionuclide therapy for pediatric patients with relapsed high-risk neuroblastoma negative on 131I-MIBG imaging - a pilot study (2024)

Abstract

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Objectives: ¹⁷⁷Lu-DOTATATE is a somatostatin analog recently approved by FDA and EC as treatment trials for advanced gastroentericpancreatic neuroendocrine tumors (GEP-NET) in adults. However, little data is found on this treatment modality for pediatric neuroblastoma. According to literature data, as much as 33% of children with neuroblastoma were negative on ¹²³I-MIBG and only 30-40% of children with relapsed neuroblastoma responded to ¹³¹I-MIBG therapy. We thus aim to investigate whether ¹⁷⁷Lu-DOTATATE therapy could be a potential option for children with relapsed neuroblastoma and who were negative on ¹³¹I-MIBG/¹²³I-MIBG but positive on pretreatment ⁶⁸Ga-DOTATATE PET/CT. We focused on lesion detection sensitivity and critical organ dosimetry in this pilot study.

Methods: From April to November 2017, children with Neuroblastoma Staging System stage IV and relapsed disease were enrolled into this study. They underwent both ¹³¹I-MIBG scintigraphy and ⁶⁸Ga-DOTATATE PET/CT to evaluate their pretreatment disease status in terms of lesion detection sensitivity and tracer avidity. Tracer avidity for both scans was qualitatively scored: 0=no uptake, 1=equivocal uptake, 2=uptake >surrounding background but <liver, 3=uptake >liver. Patients would proceed to ¹⁷⁷Lu-DOTATATE therapy if tumors were avid for ⁶⁸Ga-DOTATATE with score >2 and any of the following criteria: (1) all lesions non-avid for ¹³¹I-MIBG, (2) missed detection of metastasis in an entire organ-system on ¹³¹I-MIBG imaging, (3) tumors avid for both tracers but with ¹³¹I-MIBG score <1. Post-treatment ¹⁷⁷Lu-DOTATATE SPECT/CT (window, 113 and 208±15% KeV, 30 projections, 180°, 20 s/projection, 128×128) was performed at 4, 24 and 48 h post injection. Lesion concordance between ⁶⁸Ga-DOTATATE PET/CT and ¹⁷⁷Lu-DOTATATE SPECT/CT was checked, and absorbed dose in kidney and marrow (critical organs) was measured.

Results: 6 children (3 boys, 3 girls; age range: 1.5-7 y, median: 5 y) who qualified the selection criteria proceeded to ¹⁷⁷Lu-DOTATATE therapy. All (6/6) were previously treated by surgery and multiple lines of chemotherapy; 4/6 underwent bone marrow transplant and 2/6 radiotherapy. All children (6/6) had tumors strongly avid for ⁶⁸Ga-DOTATATE. 5/6 children had metastases in bone, 3/6 in lymph node, 2/6 in lung and 1/6 in soft tissue. The lesion SUV_max in bone was 7.3±3.3, lymph node 5.1±1.0, lung 2.2±0.6, soft tissue 3.9±0.4. However, only 2/6 (33%) children showed very mild ¹³¹I-MIBG uptake (score 1) in a few bone lesions substantially less than ⁶⁸Ga-DOTATATE PET/CT. A total of 12 therapies were given (IA=3.13±0.76 GBq): 2 children had 3 therapies, 2 had 2 therapies and 2 had 1 therapy. All ⁶⁸Ga-DOTATATE-avid lesions showed concordant high uptake on post-therapy ¹⁷⁷Lu-DOTATATE SPECT/CT. The absorbed doses in right kidney (range: 2.03-2.94 Gy, mean: 2.42±0.38 Gy), left kidney (range: 2.03-2.49 Gy, mean: 2.24±0.20 Gy) and bone marrow (range: 0.03-0.18 Gy, mean: 0.09±0.06 Gy) were all within the dose tolerance (kidney: 26 Gy, marrow: 2 Gy). Post-therapy ⁶⁸Ga-DOTATATE PET/CT in 2 children who completed treatment showed partial metabolic response (SUV_max reduction 49% & 65%; tumor volume shrinkage 75% & 26%). Conclusions: ⁶⁸Ga-DOTATATE PET/CT has superior detection sensitivity compared with ¹³¹I-MIBG in pediatric patients with relapsed advanced neuroblastoma, and ¹⁷⁷Lu-DOTATATE therapy is effective and safe. Further extension of this pilot study to a larger cohort may be considered.