131I-MIBG Therapy Research Articles

131I-mIBG Therapy in the Management of High-Risk Neuroblastoma: A Retrospective Study from a Tertiary Level Hospital in South India

Abstract Introduction Neuroblastoma is the most common extracranial solid tumor in childhood. The data on the treatment experience with 131iodine-meta-iodo-benzyl-guanidine (131I-mIBG) and clinical outcome data are meager from India. Objectives This article studies the efficacy and treatment outcomes in patients treated with 131I-mIBG in high-risk neuroblastoma. Materials and Methods The study group consisted of 201 consecutive patients (aged between 1 and 15 years) with biopsy-proven neuroblastoma who underwent 131I-mIBG scans from 2012 to 2022. The majority of these children had a disease that was inoperable or had poor response to chemotherapy. Patients with positive scintigraphy were considered for therapy with 131I-mIBG. The findings were analyzed and correlated with the final diagnosis and outcomes obtained from survival during follow-up and reviewing patient records. Results Thirty-nine children, 22 males and 17 females, with a median age of 4 years had positive 131I-mIBG scintigraphy. Intra-abdominal primary lesions and osseous lesions were the most common sites of uptake on 131I-mIBG scan. Of these, 13 had upfront chemotherapy and 26 had surgery followed by chemotherapy. All the patients underwent therapy with 131I-mIBG. Fourteen patients had multiple therapies while the remaining 25 had only one therapy. Eight patients had no follow-up, and 13 had disease relapse. The remaining 18 had regression of disease which was confirmed by follow-up 131I-mIBG scintigraphy and with bone scintigraphy in patients with osseous metastases. Conclusion 131I-mIBG scintigraphy should be preferred in intermediate and high-risk neuroblastoma to know the extent of the disease and also for patient selection for early therapy with 131I-mIBG. It holds significant utility in the management of metastatic neuroblastoma, facilitating palliative pain relief and tumor size reduction in inoperable or metastatic disease.

Evaluating the diagnostic efficacy of whole-body MRI versus 123I-mIBG/131I-mIBG imaging in metastatic pheochromocytoma and paraganglioma

This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine (mIBG) imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and 123I-mIBG as a pretreatment screening for 131I-mIBG therapy. Two expert reviewers evaluated WB-MRI, 123I-mIBG images, and post-therapy 131I-mIBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)—area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in 123I-mIBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy 131I-mIBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the mIBG images.

Aurora Kinase A inhibition enhances DNA damage and tumor cell death with 131I-MIBG therapy in high-risk neuroblastoma

BackgroundNeuroblastoma is the most common extra-cranial pediatric solid tumor. 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 131I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma.ResultsUsing an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of 131I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels.ConclusionThe combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.

Effects of Peptide Receptor Radiotherapy in Patients with Advanced Paraganglioma and Pheochromocytoma: A Nation-Wide Cohort Study.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours that originate from chromaffin cells within the adrenal medulla or extra-adrenal sympathetic ganglia. Management of disseminated or metastatic pheochromocytomas and paragangliomas continues to pose challenges and relies on limited evidence. In this study, we report retrospective data on median overall survival (OS) and median progression-free survival (PFS) for all Danish patients treated with peptide receptor radionuclide therapy (PRRT) with 177Lu-Dotatate or 90Y-Dotatate over the past 15 years. One standard treatment of PRRT consisted of 4 consecutive cycles with 8-14-week intervals. We included 28 patients; 10 were diagnosed with pheochromocytoma and 18 with paraganglioma. Median age at first PRRT was 47 (IQR 15-76) years. The median follow-up time was 31 (IQR 17-37) months. Eight patients died during follow-up. Median OS was 72 months, and 5-year survival was 65% with no difference between pheochromocytoma and paraganglioma. Patients with germline mutations had better survival than patients without mutations (p = 0.041). Median PFS after the first cycle of PRRT was 30 months. For patients who previously received systemic treatment, the median PFS was 19 months, compared with 32 months for patients with no previous systemic treatment (p = 0.083). The median OS of around 6 years and median PFS of around 2.5 years found in this study are comparable to those reported in previous studies employing PRRT. Based on historical data, the efficacy of PRRT may be superior to 131I-MIBG therapy, and targeted therapy with sunitinib and PRRT might therefore be considered as first-line treatment in this patient group.

Increasing Catecholamine Secretion Through NPY in Pheochromocytomas With False-Negative 123 I-MIBG Scintigraphy.

123 I-MIBG has been well established as a functional imaging tool, and 131 I-MIBG therapy is being considered for catecholamine-secreting tumors. Tumors with the characteristics of a noradrenergic biochemical phenotype, small, malignant, metastatic, extra-adrenal, bilateral, and hereditary, especially SDHx -related tumors, are reported to correlate with reduced MIBG uptake. However, the potential molecular mechanisms influencing MIBG uptake have been poorly studied. To identify critical genes that may enhance MIBG accumulation in pheochromocytomas (PCCs), we performed RNA-seq analyses for 16 operated patients with PCCs (6 MIBG-negative and 10 MIBG-positive) combined with RT-qPCR for 27 PCCs (5 MIBG-negative and 22 MIBG-positive) and examined primary cultures of the surgical tissues. In the present study, 6 adrenal nodules of 66 nodules surgically removed from 63 patients with PCCs (9%) were MIBG negative. MIBG, a guanethidine analog of norepinephrine, can enter chromaffin cells through active uptake via the cellular membrane, be deposited in chromaffin granules, and be released via Ca 2+ -triggered exocytosis from adrenal chromaffin cells. When we compared expression of several catecholamine biosynthesis and secretion-associated genes between MIBG-negative and MIBG-positive tumors using transcriptome analyses, we found that neuropeptide Y, which is contained in chromaffin granules, was significantly increased in MIBG-negative tumors. NPY stimulated norepinephrine secretion dose-dependently in primary cell culture derived from MIBG-positive PCC. In our study, MIBG-negative PCCs were all norepinephrine-hypersecreting tumors. These data indicate that NPY upregulation in PCCs may stimulate chromaffin granule catecholamine secretion, which is associated with false-negative 123 I-MIBG scintigraphy.

The Impact of 131I-Metaiodobenzylguanidine as a Conditioning Regimen of Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Neuroblastoma.

The optimal conditioning regimen of tandem high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for high-risk neuroblastoma (HR-NBL) has not been established. The efficacy of 131I-MIBG therapy is under exploration in newly diagnosed HR-NBL patients. Here, we compared the outcomes of tandem HDC/ASCT between the 131I-MIBG combination and non-MIBG groups. We retrospectively analyzed the clinical data of 33 HR-NBL patients who underwent tandem HDC/ASCT between 2007 and 2021 at the Seoul National University Children's Hospital. The median age at diagnosis was 3.6 years. 131I-MIBG was administered to 13 (39.4%) of the patients. Thirty patients (90.9%) received maintenance therapy after tandem HDC/ASCT, twenty-two were treated with isotretinoin ± interleukin-2, and eight received salvage chemotherapy. The five-year overall survival (OS) and event-free survival (EFS) rates of all patients were 80.4% and 69.4%, respectively. Comparing the 131I-MIBG combined group and other groups, the five-year OS rates were 82.1% and 79.7% (p = 0.655), and the five-year EFS rates were 69.2% and 69.6% (p = 0.922), respectively. Among the adverse effects of grade 3 or 4, the incidence of liver enzyme elevation was significantly higher in the non-131I-MIBG group. Although tandem HDC/ASCT showed promising outcomes, the 131I-MIBG combination did not improve survival rates.

Norepinephrine transporter and vesicular monoamine transporter 2 tumor expression as a predictor of response to 131 I-MIBG in patients with relapsed/refractory neuroblastoma.

Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to 131 I-MIBG therapy in patients with neuroblastoma. Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with 131 I-MIBG. A composite protein expression H-score was determined by multiplying a semi-quantitative intensity value (0-3+) by the percentage of tumor cells expressing the protein. Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for <PR; p=.0014). VMAT2 H-score was not significantly associated with PR or higher versus less than PR, though patients with PR or higher had lower VMAT2 staining intensity (p=.005). VMAT2 H-score was significantly lower in patients with complete response (median 40 vs. 210 for patients with <complete response; p=.0049). VMAT2 H-scores were significantly higher in ganglioneuroblastoma (vs. neuroblastoma; p=.037), differentiated/poorly differentiated tumors (vs. undifferentiated; p=.0047), and tumors lacking MYCN amplification (vs. MYCN amplified; p=.0011). Markers of lower NET and VMAT2 protein expression are associated with higher likelihood of response to 131 I-MIBG therapy in patients with relapsed/refractory neuroblastoma. Increased VMAT2 protein expression is associated with a more differentiated disease phenotype.

The Plasma Membrane Monoamine Transporter is Highly Expressed in Neuroblastoma and Functions as an mIBG Transporter.

Neuroblastoma (NB) is a pediatric cancer with low survival rates in high-risk patients. 131I-mIBG has emerged as a promising therapy for high-risk NB and kills tumor cells by radiation. Consequently, 131I-mIBG tumor uptake and retention are major determinants for its therapeutic efficacy. mIBG enters NB cells through the norepinephrine transporter (NET), and accumulates in mitochondria through unknown mechanisms. Here we evaluated the expression of monoamine and organic cation transporters in high-risk NB tumors and explored their relationship with MYCN amplification and patient survival. We found that NB mainly expresses NET, the plasma membrane monoamine transporter (PMAT), and the vesicular membrane monoamine transporter 1/2 (VMAT1/2), and that the expression of these transporters is significantly reduced in MYCN-amplified tumor samples. PMAT expression is the highest and correlates with overall survival in high-risk NB patients without MYCN amplification. Immunostaining showed that PMAT resides intracellularly in NB cells and co-localizes with mitochondria. Using cells expressing PMAT, mIBG was identified as a PMAT substrate. In mitochondria isolated from NB cell lines, mIBG uptake was reduced by ∼50% by a PMAT inhibitor. Together, our data suggest that PMAT is a previously unrecognized transporter highly expressed in NB and could impact intracellular transport and therapeutic response to 131I-mIBG. SIGNIFICANCE STATEMENT: This study identified that plasma membrane monoamine transporter (PMAT) is a novel transporter highly expressed in neuroblastoma and its expression level is associated with overall survival rate in high-risk patients without MYCN amplification. PMAT is expressed intracellularly in neuroblastoma cells, transports meta-iodobenzylguanidine (mIBG) and thus could impact tumor retention and response to 131I-mIBG therapy. These findings have important clinical implications as PMAT could represent a novel molecular marker to help inform disease prognosis and predict response to 131I-mIBG therapy.

Neuroblastoma: Can lessons from the past help to improve the future?

Background. The outcome of patients with neuroblastoma in South Africa has always been very poor. We conducted a retrospective study in one state-funded paediatric oncology unit (POU), to describe the clinical course, evaluate prognostic factors and report outcomes of patients with neuroblastoma.Methods. We analysed routine data from one POU, gathered between 1993 and 2018. Kaplan-Meier curves were used to illustrate 2-year survival rates and to evaluate possible prognostic factors.Results. Data from 87 patients were included and analysed. The median age was 41 months. The majority of the patients presented with stage 4 disease (77%). The most common presenting symptoms were bone pain, loss of weight, and abdominal distention. Chemotherapy was administered to 74 patients, and only 5 patients (6%) received palliative chemotherapy as first-line treatment. Only 18 of the 87 patients had surgery (21%) and 13 of 87 had radiation (15%), while 10 patients received palliative radioactive iodine (131I-miBG) therapy. Patients with ferritin levels &gt;120 ng/dL did not have a poorer outcome, and those with a raised lactate dehydrogenase (LDH) level displayed a shorter survival time but it was not statistically significant. The 2-year overall survival was 24% for the whole cohort and 16% for the stage 4 patients at diagnosis.Conclusion. Neuroblastoma is a disease with a dismal outcome in our POU, mostly as a result of late presentation. To improve prognosis the focus should be on recognising danger signs to ensure early diagnosis and referral. We recommend adding danger signs for childhood cancer to the Integrated Management of Childhood Illness (IMCI) strategy in an attempt to improve early recognition and diagnosis of childhood cancer.

Proposed MIBG Scan-Based Tumor Response Criteria of High-Specific-Activity 131 I-MIBG Therapy in Metastatic Pheochromocytoma/Paraganglioma.

High-specific-activity 131 I-MIBG (Azedra) is the only Food and Drug Administration-approved therapy for metastatic pheochromocytomas and paragangliomas, which are rare neuroendocrine tumors with limited treatment options. Based on our experience, we proposed here functional imaging-based tumor response criteria for these patient cohorts. Each response category was illustrated with typical sample cases, and clinical correlation was provided.

Efficacy and Safety of 124I-MIBG Dosimetry-Guided High-Activity 131I-MIBG Therapy of Advanced Pheochromocytoma or Neuroblastoma.

We aim to evaluate the efficacy and safety of 124I-metaiodobenzylguanidine (MIBG) dosimetry-guided high-activity 131I-MIBG therapy of advanced pheochromocytoma or neuroblastoma. Methods: Fourteen patients with advanced pheochromocytoma or neuroblastoma, age 9-69 y, underwent 124I-MIBG PET scans and whole-body retention measurements to assess the whole-body dose as a surrogate of bone marrow toxicity and tumor (absorbed) dose per unit of administered activity. Dosimetry results together with individual patient characteristics were combined to guide a single therapeutic activity to achieve a high tumor dose without exceeding toxicity threshold. Toxicity was assessed for hematologic, hepatic, and renal function. Response was evaluated by RECIST, International Society of Pediatric Oncology Europe Neuroblastoma-like score, change in PET uptake, and quantitative PET parameters (SUVmax, SUVpeak, metabolic tumor volume, total lesion glycolysis), as well as visual decrease in number or in visual intensity of lesions on baseline to follow-up 124I-MIBG PET/CT. Results: The average therapeutic activity was 14 GBq. Eleven of 14 patients (79%) received each more than 10 GBq. One male patient was treated with a single activity of 50 GBq. Three patients were treated with lower activities between 3.5 and 7.0 GBq. Median overall survival was 85 mo (95% CI), and median progression-free survival was 25 mo (95% CI). Four (29%) and 5 (36%) patients demonstrated response (complete response or partial response) by RECIST and functional imaging, respectively. One patient exceeded whole-body dose of 2 Gy and demonstrated grade 3 hematologic toxicity, which resolved spontaneously within 12 mo after the therapy without the need for further treatment. Three patients (21%) demonstrated transient grade 1 renal toxicity. Conclusion: 124I-MIBG dosimetry-guided high-activity 131I-MIBG therapy in patients with advanced pheochromocytoma or neuroblastoma resulted in durable responses with a low rate of manageable adverse events. Efficacy of 124I-MIBG-guided activity escalation should further be assessed in a prospective setting.

SHDB mutant functional metastatic paraganglioma: The efficacy of Lutetium-177 DOTATE

Abstract Introduction Therapeutic options for metastatic paraganglioma (PGL) are limited, especially in the presence of uncontrolled secondary hypertension (HTN). Early findings from Lutetium-177 (Lu-177) DOTATE show promise for efficacy, although data on HTN control and survival are uncertain. Herein, we presented the successful treatment of a patient with metastatic PGL and uncontrolled HTN with Lu-177 DOTATE. Clinical Case A 16-year-old woman was admitted to the emergency department with severe headache, nausea and vomiting. She also reported stomach and low back pain for three months. The patient's blood pressure was 220/140 mmHg and a sodium nitroprusside infusion was started to treat the hypertensive crisis. On physical examination she had abdominal tenderness. A computer tomography (CT) examination revealed 6 cm mass, multiple metastatic nodular lesions in the lung and liver, as well as lytic lesions in all bones, and metastatic lymph nodes in thorax and abdomen. She is referred to our department for further evaluation HTN. Laboratory examinations revealed that plasma norepinephrine 24926 ng/L (70–480), 24-hour urine norepinephrine 1335 µg/day (20–81), metanephrine 534 µg/day (52–341), 3-metoksitiramine 771 µg/day (0–451), normetanephrine 20456 µg/day (88–444). Other laboratory findings were normal range. MIBG I131 scan which showed pathological uptake of MIBG was demonstrated in the regions described on CT. Genetic panel by next-generation sequencing (NGS) identify germline mutation and she had heterozygous mutations in SHDB (c.725 G&amp;gt;A) and BUB1B (c.1378 C&amp;gt;T). Surgical treatment was performed, and pathological finding reported 6cm mass, Ki-67 labeling index: %2, chromogranin A diffuse positive and there was vascular invasion. It was confirmed to be malignant PGL. 131I-MIBG therapy couldn't be given because of drugs interaction that used by patient. She received 13 cycles chemotherapy (cyclophosphamide, vincristine, dacarbazine) and palliative radiotherapy to metastatic bone lesions. She continued, however, to suffer from low back pain and HTN. Rising plasma and urine catecholamine levels. Therefore, conventional chemotherapy had been discontinued and he was commenced on Lu-DOTATATE therapy. Up to now, she has received 2 cycles at intervals of three months. Her clinical response was excellent with gradual improvement of symptoms and quality of life. Blood pressure is now within normal values without medication. There was significant reduction in the size of overall metastatic disease on Ga-68 DOTATE scanning. Conclusion Lu-177 DOTATE has potential advantages (drug interaction, radiation-safety) compared with 131I-MIBG therapy and chemotherapy. Our case demonstrates significant clinical and biochemical success in patients with metastatic PGL in addition to excellent disease management with low toxicity from PRRT. Lu-177 DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic PGL.

Nurses' Experiences Caring for Children With Neuroblastoma Receiving 131I-Metaiodobenzylguanidine Therapy: A Qualitative Descriptive Study.

Background: Neuroblastoma, the most common extra-cranial solid tumor found in children, carries a high mortality rate due to challenges with metastatic disease at diagnoses and relapse. 131I-Metaiodobenzylguanidine (I-MIBG) therapy provides targeted radiotherapy to treat neuroblastoma, but requires children to be isolated for radiation exposure, with limited access to the healthcare team while hospitalized. There is minimal research outlining the nurses' perspectives on caring for this patient population. Therefore, the aim of this study was to describe the nurses' experiences caring for children receiving 131I-MIBG therapy, focusing on nursing care, challenges, radiation exposure, and preparation. Methods: Ten nurses were recruited using purposeful sampling for this qualitative descriptive study. Semi-structured interview guides and conventional qualitative content analysis guided the data collection and analysis. Results: Nurses overwhelmingly felt isolated from their patients and a decreased sense of connection with the child. Although nurses felt prepared, they had more anxiety with the first patient experience and identified that parent engagement was essential. Overall, nurses shared they had support from written materials outlining the protocols, and members of the multidisciplinary team. More concern for radiation exposure was expressed by nurses of childbearing age and with handling bodily fluids. Discussion: Findings suggest that nurses would benefit from simulation experiences to help prepare for radiation exposure safety, strategies to engage the family in the child's care, and interacting with a child in single-room isolation. Because programs differ around the US, additional research exploring nurses' experiences is warranted to evaluate the best successes in providing 131I-MIBG therapy.

Modulation of Radiation Biomarkers in a Randomized Phase II Study of 131I-MIBG With or Without Radiation Sensitizers for Relapsed or Refractory Neuroblastoma

131I-metaiodobenzylguanidine (131I-MIBG) has demonstrated efficacy as a single agent in neuroblastoma. Recent trials have focused on 131I-MIBG combination strategies, though little is known about the effect of putative radiosensitizers on biological markers of radiation exposure. NANT2011-01 evaluated 131I-MIBG therapy alone (arm A) or in combination with vincristine/irinotecan (arm B) or vorinostat (arm C) for patients with relapsed or refractory neuroblastoma. Blood samples were collected before and after 131I-MIBG infusion to determine levels of radiation-associated biomarkers (transcript and protein). The association of biomarker with treatment arm, clinical response, and treatment toxicity was analyzed. The cohort included 99 patients who had at least 1 biomarker available for analysis. Significant modulation in most biomarkers between baseline, 72, and 96 hours following 131I-MIBG was observed. Patients in arm C had the lowest degree of modulation in FLT3 ligand protein. Lower baseline BCL2 transcript levels were associated with higher overall response. Patients with greater increases in FLT3 ligand at 96 hours after 131I-MIBG therapy were significantly more likely to have grade 4 thrombocytopenia. Peripheral blood gene expression of the BCL2 family of apoptotic markers (BCL2L1 and BAX transcripts) was significantly associated with grade 4 hematologic toxicity. RNA sequencing demonstrated little overlap in the top modulated peripheral blood transcripts between randomized arms. Peripheral blood biomarkers relevant to radiation exposure demonstrate significant modulation after 131I-MIBG and concomitant radiation sensitizers affect extent of modulation. Biomarkers related to hematopoietic damage and apoptosis were associated with hematologic toxicity.

OR29-3 High-specific-activity Iodine 131 Metaiodobenzylguanidine for the Treatment of Advanced Pheochromocytoma and Paraganglioma: A Real-world Study

Abstract Introduction Metastatic pheochromocytomas/paragangliomas (mPPGLs) are rare tumors with limited treatment options. High-specific-activity 131I-meta-iodobenzylguanidine (HSA 131I-MIBG) is the only approved therapy for mPPGLs. We summarized the efficacy and safety profile of HSA 131I-MIBG in patients with mPPGL. Methods This is a retrospective cohort study in patients with mPPGL treated with HSA 131I-MIBG on label at a tertiary cancer center. The primary endpoint was radiographic treatment response determined with CT/MRI according to RECIST v1.1 and 123 I-MIBG scan. Secondary endpoints were blood pressure changes and HSA 131I-MIBG related adverse events. We correlated responses with the genetic background as an exploratory endpoint. Results Twenty-four patients were treated including 15 men (62%). Median age at the time of treatment was 44 years (range 18–82). Twenty-three patients had distant metastases and one patient had an unresectable primary tumor. Seventeen patients (70%) had hormonally active tumors and 17 patients (70%) were on antihypertensive medications before HSA 131I-MIBG therapy [7 patients on alpha-blockers only and 10 on combination antihypertensive therapy]. Thirteen patients (54%) previously received antineoplastic treatment. Eleven patients (46%) received one dose of HSA 131−I-MIBG, the remaining received two doses. Median duration of follow-up was 15 months (range 2–52). In 23 evaluable patients, radiographic responses included: 2 complete responses (CR), 10 partial responses (PR), 8 stable diseases (SD), 2 mixed responses (MR), and 1 progressive disease (PD) yielding disease control rate (DCR) of 87%. Median time to response was 12.5 months (95% CI, 4.6 to 25.1). Radiographic responses in patients with sporadic disease were [6/11 SD, 3/11 PR, 1/11 MR, 1/11 PR], while the response in patients with a genetic mutation (SDHB, VHL, RET) was [2/12 CR, 7/12 PR, 2/12 SD, 1/12 MR]. In 17 hormonally active tumors, plasma metanephrines normalized in 3(18%), improved by 50% in 5(29%), increased in 4(24%), 4 patients (24%) had no repeat levels and one had stable levels. Blood pressure was evaluable in 22 (92%) patients. Blood pressure normalized in 9 patients (41%) leading to discontinuation of antihypertensive therapy. One patient had an improvement in the blood pressure leading to a reduction of antihypertensive medications. The most common adverse events were grade I/II nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Grade III/IV myelosuppression was seen in 3/24 (12%) patients. One patient had fatal pneumonitis, and one patient developed fatal gastrointestinal bleeding a month after treatment with unclear attribution to HSA 131 −I-MIBG. Conclusions In mPPGL, HSA 131I-MIBG is associated with high DCR regardless of underlying genetic mutation. Severe adverse events are infrequent but can be fatal. Presentation: Tuesday, June 14, 2022 10:15 a.m. - 10:30 a.m.

Case Series: Primary / neo-adjuvant 131I-MIBG therapy as a safe and effect treatment in the management of pheochromocytoma / paraganglioma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Release criteria and exposure of caregivers and public after discharge of patients undergoing 131I-MIBG, 131I-NaI and 177Lu-DOTATATE therapies

Release criteria and exposure of caregivers and public after discharge of patients undergoing 131I-MIBG, 131I-NaI and 177Lu-DOTATATE therapies

Modulation of radiation biomarkers in a randomized phase II study of 131I-MIBG with or without radiation sensitizers for relapsed or refractory neuroblastoma: A report from the NANT Consortium.

10026 Background: 131I-metaiodobenzylguanidine (131I-MIBG) has demonstrated efficacy as a single agent for patients with neuroblastoma. Recent trials have focused on 131I-MIBG combination strategies, though little is known about the impact of combination agents on markers of radiation exposure. Methods: NANT11-01 (NCT02035137) was a multicenter, open label, randomized phase II clinical trial that evaluated 131I-MIBG therapy alone (Arm A) or in combination with vincristine/irinotecan (Arm B) or vorinostat (Arm C) for patients with resistant/relapsed neuroblastoma. We collected blood samples at baseline, 72 hours, 96 hours, and 15 days after 131I-MIBG infusion and determined levels of plasma FLT3 ligand, serum amylase, and gene expression for selected RNA transcripts (apoptosis, DNA damage response and cell cycle related). We evaluated marker association with treatment arm, clinical response using NANT response criteria, toxicity, and whole-body radiation dose. Results: The cohort included 99 patients who had at least one biomarker available for analysis (32 Arm A; 35 Arm B; 32 Arm C). We observed both positive and negative significant modulation in most biomarkers between baseline, 72 hours, and 96 hours following 131I-MIBG. Patients in Arm C had the lowest degree of modulation in FLT3 ligand. Elevated baseline levels of FLT3 ligand were significantly associated with improved Curie response but not overall response. Lower baseline BCL2 levels were associated with higher overall and Curie response. Patients with increased FLT3 ligand at 96 hours after 131I-MIBG therapy were significantly more likely to have grade 4 thrombocytopenia.Peripheral blood gene expression of the BCL2 family of apoptotic markers (BCL2/L1 and BAX) was significantly associated with grade 4 hematological toxicity. Whole-body radiation dose and PRKDC fold change at 72 hours were significantly correlated. No other individual biomarkers were correlated with whole body radiation dose at 72 or 96 hours post 131I-MIBG. Conclusions: Peripheral blood biomarkers relevant to radiation exposure demonstrate significant modulation over time after 131I-MIBG treatment. Biomarkers related to hematopoietic damage and apoptosis were associated with hematological toxicity. Patients treated with vorinostat and 31I-MIBG had differential modulation of FLT3-ligand Further use of these biomarkers may improve our ability to care for patients treated with 131I-MIBG.

The efficacy and safety of Iodine-131-metaiodobenzylguanidine therapy in patients with neuroblastoma: a meta-analysis

ObjectiveNeuroblastoma is a common extracranial solid tumor of childhood. Recently, multiple treatments have been practiced including Iodine-131-metaiodobenzylguanidine radiation (131I-MIBG) therapy. However, the outcomes of efficacy and safety vary greatly among different studies. The aim of this meta-analysis is to evaluate the efficacy and safety of 131I-MIBG in the treatment of neuroblastoma and to provide evidence and hints for clinical decision-making.MethodsMedline, EMBASE database and the Cochrane Library were searched for relevant studies. Eligible studies utilizing 131I-MIBG in the treatment of neuroblastoma were included. The pooled outcomes (response rates, adverse events rates, survival rates) were calculated using either a random-effects model or a fixed-effects model considering of the heterogeneity.ResultsA total of 26 clinical trials including 883 patients were analyzed. The pooled rates of objective response, stable disease, progressive disease, and minor response of 131I-MIBG monotherapy were 39%, 31%, 22% and 15%, respectively. The pooled objective response rate of 131I-MIBG in combination with other therapies was 28%. The pooled 1-year survival and 5-year survival rates were 64% and 32%. The pooled occurrence rates of thrombocytopenia and neutropenia in MIBG monotherapy studies were 53% and 58%. In the studies of 131I-MIBG combined with other therapies, the pooled occurrence rates of thrombocytopenia and neutropenia were 79% and 78%.Conclusion131I-MIBG treatment alone or in combination of other therapies is effective on clinical outcomes in the treatment of neuroblastoma, individualized 131I-MIBG is recommended on a clinical basis.

Metastatic Extra-Adrenal Pheochromocytoma with Single Kidney and Renal Compromise: A Case Report of Excellent Response, Tolerability, and Outcome to a Modified Regimen of 131I-mIBG, and Decision-Making between 131I-mIBG Therapy and PRRT

AbstractDetermining the choice and the goal is key element for decision-making of a systemic radionuclide therapy. They should be clearly defined in deciding and individualizing the dose and regimen. For iodine-131 metaiodobenzylguanidine (131I-mIBG) therapy, the important considerations during dose fractionation include disease burden, tumor biology, functional symptoms, and associated comorbidities, all of which are important determinants for the intent and course of treatment. Herein, we present the case of a 67-year-old elderly female with highly functional metastatic recurrent extra-adrenal pheochromocytoma (presenting 42 years after the primary surgery and 32 years following excision of pararenal recurrence) with multiple comorbidities including single kidney and borderline renal compromise, treated successfully with a relatively lower dose of 131I-mIBG (cumulative dose of 22.2 GBq in four cycles with a mean dose of 5.7 GBq per therapy cycle). The excellent tumor burden reduction, hormonal tumor marker response, and most importantly asymptomatic status could be achieved with the administered dose. On follow-up, none of the pretherapeutic parameters (including renal function) showed any further derangement compared with the baseline during next 24 months following the treatment. All cycles were well tolerated with only reversible hematological toxicity that normalized without any active intervention. The report is intended to provide some guidance for future therapeutic regimens.