Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens.

Serotonergic hallucinogens induce profound changes in perception and cognition. The characteristic effects of hallucinogens are mediated by 5-HT2A receptor activation. One class of hallucinogens are 2,5-dimethoxy-substituted phenethylamines, such as the so-called 2C-X compounds 2,5-dimethoxy-4-bromophenethylamine (2C-B) and 2,5-dimethoxy-4-iodophenethylamine (2C-I). Addition of an N-benzyl group to phenethylamine hallucinogens produces a marked increase in 5-HT2A-binding affinity and hallucinogenic potency. N-benzylphenethylamines ("NBOMes") such as N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (25I-NBOMe) show subnanomolar affinity for the 5-HT2A receptor and are reportedly highly potent in humans. Several NBOMEs have been available from online vendors since 2010, resulting in numerous cases of toxicity and multiple fatalities. This chapter reviews the structure-activity relationships, behavioral pharmacology, metabolism, and toxicity of members of the NBOMe hallucinogen class. Based on a review of 51 cases of NBOMe toxicity reported in the literature, it appears that rhabdomyolysis is a relatively common complication of severe NBOMe toxicity, an effect that may be linked to NBOMe-induced seizures, hyperthermia, and vasoconstriction.

High-performance dendritic contrast agents for X-ray computed tomography imaging using potent tetraiodobenzene derivatives.

The use of computed tomography (CT) for vascular imaging is critical in medical emergencies requiring urgent diagnostic decisions, such as cerebral ischemia and many cardiovascular diseases. Small-molecule iodinated contrast media are often injected intravenously as radiopaque agents during CT imaging to achieve high contrast enhancement of vascular systems. The rapid excretion rate of these agents is overcome by injecting a significantly high dose of iodine, which can have serious side effects. Here we report a simple method to prepare blood-pool contrast agents for CT based on dendrimers for the first time using tetraiodobenzene derivatives as potent radiopaque moieties. Excellent in vivo safety has been demonstrated for these small (13-22nm) unimolecular water-soluble dendritic contrast agents, which exhibit high contrast enhancement in the blood-pool and effectively extend their blood half-lives. Our method is applicable to virtually any scaffold with suitable surface groups and may fulfill the current need for safer, next-generation iodinated CT contrast agents.

Cytotoxic Effects of a Novel Thialo Benzene Derivative 2,4-Dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) in L929 Cells.

The aim of this study was to compare the cytotoxic effects of a newly synthesized thialo benzene derivative 2,4-dithiophenoxy-1-iodo-4-bromobenzene (C18H12S2IBr) and a well-known antifungal agent, fluconazole, in L929 cells. L929 cells were treated with 250, 500, or 1000 µg/mL of C18H12S2IBr and with the same doses of fluconazole. Cytotoxicity tests including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) leakage, and protein content were compared. Glucose and lactate concentrations were measured to determine alterations in metabolic activity. Apoptosis was investigated by TUNEL test and results were supported with survivin enzyme-linked immunosorbent assay. Treatment with C18H12S2IBr resulted in a concentration-dependent cytotoxicity as indicated by MTT, LDH leakage assay, and decreased protein concentration. The loss of cell viability and the increased LDH leakage in 500 µg/mL and 1000 µg/mL C18H12S2IBr and fluconazole groups indicated cell membrane damage and necrotic cell death. In all groups, metabolic activities were altered but apoptosis was not induced. We have previously investigated lower doses of C18H12S2IBr; there was no cytotoxicity in L929 cells. In this study, higher doses caused cytotoxicity and alterations in metabolic activity . When we consider the similar results obtained from fluconazole and especially the lowest dose of C18H12S2IBr, this newly synthesized compound may be a good alternative antifungal agent.

Prognostic value of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid single-photon emission computed tomography in diabetic patients with suspected ischemic heart disease.

BACKGROUND: Because of their high risk for cardiovascular events, we investigated the role of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) SPECT in evaluating the prognosis of diabetic patients with suspected coronary heart disease. METHODS AND RESULTS: We retrospectively registered 186 diabetic patients with suspected coronary heart disease, but no previous diagnosis of heart disease, who had been examined by BMIPP and thallium (TL) dual SPECT. They were followed for over 2 years. The dual SPECT images were scored to obtain summed defect scores for each SPECT image (BMDS, TLDS and mismatch score [MS]). The primary endpoint was the first incidence of all-cause cardiac events. The secondary endpoint was cardiac death. Clinical classical risk factors in addition to the stage of chronic kidney disease (CKD), as well as cardiac function, were included in the prognostic analysis. Cardiac events occurred in 39 patients, including 8 cardiac deaths. Kaplan-Meier analysis revealed significantly more frequent cardiac event rates in patients with than without MS ≥5 or BMDS ≥6 (P<0.0001). Cox hazard multivariate analysis showed that MS and CKD stage or BMIPP and CKD stage were independent predictors. Only hemodialysis was a significant prognostic indicator for cardiac death. CONCLUSIONS: BMIPP SPECT when combined with CKD stage accurately predicts cardiac events among diabetic patients with suspected ischemic heart disease.

Acute liver necrosis induced by iodine-131-MIBG in the treatment of metastatic carcinoid tumors.

Iodine-131-metaiodobenzylguanidine (MIBG) is used in the treatment of carcinoid tumors. Temporary palliation with complete subjective symptomatic response has been reported in these patients. This treatment is usually well tolerated and side-effects are generally limited to nausea, mild hepatic toxicity with spontaneous recovery and temporary myelosuppression. Our case report shows that repeated treatment with [131I]MIBG in a patient with extensive carcinoid liver metastasis may cause severe hepatic toxicity leading to death. Factors such as concomitant use of 5-fluorouracil and the progressive nature of the disease may have contributed to this event.

Short-term hazards of low-dose radioiodine ablation therapy in postsurgical thyroid cancer patients.

During the last two decades, there has been a trend to use low-dose I-131 ablation therapy in patients with thyroid carcinoma without metastases. However, information regarding the incidence of acute adverse reactions in patients after low-dose radioiodine therapy has not been reported. In this study, the acute radiation effects after low-dose radioiodine ablation therapy in postsurgical differentiated thyroid cancer patients was evaluated. Fifty-six patients with differentiated thyroid cancer were prospectively evaluated. None of these patients had evidence of a distant metastasis. All patients received 40 mCi (1480 MBq) I-131 MIBG orally and were evaluated for symptoms and signs by a physician on the second and seventh days after therapy. Xerostomia and nausea were the most common complaints with the same incidence rate of 5.35%. Gastralgia occurred at a frequency of 3.57%. Pain in the thyroid bed, tenderness over a parotid gland, submandibular glands, change in taste, and vomiting all were found at a frequency of 1.78%. Maximum reactions generally occurred 24-48 hours after therapy. All the symptoms except for xerostomia resolved completely in most patients within a week. In comparison with high-dose ablation therapy published in the literature, the incidence of radiation reactions in low-dose radioiodine therapy was much lower. It was concluded that in patients without lymph node or distant metastases, low-dose I-131 MIBG therapy may be recommended to avoid the high incidence of local complications after high-dose treatment.

Iodine-131-metaiodobenzylguanidine dosimetry in cancer therapy: risk versus benefit.

UNLABELLED: In the treatment of neural crest tumors, such as pheochromocytoma, with[131I]MIBG, bone marrow toxicity limits the amount of administered activity and, thus, a therapeutically useful tumor dose. METHODS: We calculated tumor doses in a series of diagnostic studies with [123I]MIBG using accurate quantification of SPECT and planar scintigraphy. By extrapolating diagnostic results to therapeutic activities of [131I]MIBG, we could compare the results with whole-body doses from a series of therapies. RESULTS: The tumor dose was DT = 2.2 mGy MBq(-1) (median value of 27 measurements, range 0.04 < or = DT < or = 20 mGy MBq(-1) and the whole-body dose in a series of 16 patients undergoing 50 therapies was DWB = 0.12 +/- 0.04 mGy MBq(-1) (mean +/- s.d.). The therapeutic ratio varied between 130 to below 10 in some patients. CONCLUSION: The results were compared with published data. We found clearly skewed distribution of tumor doses, with a majority of tumors receiving only a few mGy per MBq administered activity. In some patients, however, doses did reach 20 mGy MBq(-1).

Palliative effect of metaiodobenzylguanidine in metastatic carcinoid tumors.

PURPOSE: To evaluate the therapeutic effect of iodine-131-labeled metaiodobenzylguanidine (131I-MIBG) and unlabeled MIBG in patients with carcinoid tumor. MATERIALS AND METHODS: A therapeutic dose of 7.4 GBq (200 mCi) 131I-MIBG infused over 4 hours was administered to 30 patients with either carcinoid syndrome (n = 20) or tumor symptoms such as pain and fever due to carcinoid tumor (n = 10). In general, two courses were given, 6 weeks apart. Due to radioactivity, patients had to be isolated for 5 to 7 days. Subsequently, we studied the effect of unlabeled MIBG based on the possible pharmaceutic activity of MIBG and to avoid the isolation procedure. A doseescalation study of 8.5, 17, and 34 mg/m2 MIBG infused over 4 hours at 4-week intervals was performed in 20 patients with carcinoid syndrome who were not suitable for treatment with the radioactive compound. RESULTS: Following 131I-MIBG treatment, symptomatic responses were observed in 60% of patients (median duration, 8 months; maximum, 2 years). Side effects were mild and rapidly reversible in 16 patients, and were related to the isolation procedure in seven of these patients. Unlabeled MIBG resulted in symptomatic improvement in 60% of patients (median duration, 4.5 months). Side effects, which included changes in blood pressure, were mild and transient. Symptomatic responses were not accompanied by biochemical responses. CONCLUSION: Both MIBG treatment regimens were equally effective in the palliation of symptoms, but duration of response tended to be much longer with the radioactive compound. However, the unlabeled compound provided a simpler treatment, eg, in elderly patients and those in poor condition, without the need for isolation.

Survival of patients with neuroblastoma treated with 125-I MIBG.

Recurrent or persistent neuroblastoma in stages III and IV is usually fatal despite modern therapies. Metaiodobenzylguanidine labeled with 131-I (131-I MIBG) concentrates in most neuroblastoma and when given in doses that impart therapeutic radiation, has produced remissions in patients with these tumors. However, success with 131-I MIBG has been limited. The physical characteristics of radiation imparted by 125-I MIBG theoretically could overcome some of the limitations that restrain the therapeutic effects of 131-I MIBG in patients with neuroblastoma. Thereby, 125-I MIBG may offer advantages over 131-I MIBG in the treatment of neuroblastoma. Ten children who manifested persistent/recurrent stage III or IV neuroblastoma were given 8.3 to 30.1 GBq or 224 to 814 mCi of 125-I MIBG in a phase I-II trial. Five of the patients had progression-free survivals > 1 year (continuing in three patients), and four of these subjects are surviving 17 to 52 months after treatment with 125-I MIBG. With appropriate doses of 125-I MIBG, life-threatening toxicity can be avoided. Thus, survivals after 125-I MIBG appear to be as long or longer than those historically observed following other treatments for patients similarly afflicted with refractory neuroblastoma.

[131I]MIBG as a first line treatment in advanced neuroblastoma.

The observed response to [131I]MIBG therapy in advanced neuroblastoma after conventional therapy, the noninvasiveness of the procedure, and the high metabolic activity which is frequently observed in untreated tumors led to the concept of substituting [131I]MIBG therapy for combination chemotherapy at diagnosis prior to surgery in patients with advanced disease/high risk neuroblastoma. The objective of this approach is to reduce the tumor volume, enabling adequate surgical resection of the tumor, and to avoid toxicity and the induction of early drug resistance. Chemotherapy is reserved to treat minimal residual disease postoperatively. Thirty-one children who presented with inoperable neuroblastoma were treated according to this protocol. After an objective response to [131I]MIBG therapy at diagnosis, 19 of 27 evaluable patients (70%) had complete or > 95% resection of the primary tumor or did not require surgery at all. Only mild hematological toxicity was observed. It is concluded that [131I]MIBG therapy of neuroblastoma at diagnosis is feasible; its effectiveness in attaining operability of the primary tumor is at least equal to that of combination chemotherapy, but its toxicity is considerably less.

Treatment with meta-[131I]iodobenzylguanidine and cisplatin in stage IV neuroblastoma.

Metastatic neuroblastoma (NB) continues to have a dismal prognosis. NB is a radiosensitive tumor. Owing to its high concentration in the NB lesions, Metaiodobenzylguanidine (MIBG) has the potential for specifically delivering very large radiation doses to the malignant cells. Encouraging results have been reported with [131I]MIBG used alone in patients resistant to conventional therapy and at diagnosis. We report the first attempts to explore the integration of this new treatment modality with chemotherapy. Among the drugs effective in NB, cisplatin was chosen because of its high degree of activity against NB, its mild hematologic toxicity and the known synergism between cisplatin and radiation. Four patients, 3 with relapsed, heavily pre-treated, progressive stage IV NB, and 1 with stage IV NB at diagnosis, all with a good [131I]MIBG uptake, were investigated with the combined therapy. Two complete remissions and one partial remission were observed in the relapsed patients 4-6 weeks following only one single course of both cisplatin and [131I]MIBG at the "standard" dosage. The only toxicity was hematologic, which was significant and relatively long-lasting, but was not associated with any serious infections or bleeding tendency. The general condition of these patients during the entire study period was excellent. The 4th patient, investigated at diagnosis with a modified less intensive treatment, obtained a partial remission with a mild hematologic toxicity. The provisional conclusion of this preliminary study is that this new form of combined therapy appears very effective in heavily pretreated relapsed patients with progressive disease, and could also be investigated in refractory patients and in patients at diagnosis.

Primary hypothyroidism as a consequence of 131-I-metaiodobenzylguanidine treatment for children with neuroblastoma.

BACKGROUND: 131-I-metaiodobenzylguanidine is a radioiodinated compound selectively concentrated by cells of neuroectodermal origin, including neuroblastoma cells, for this reason it may represent a promising treatment modality for neuroblastoma in childhood. Although a potential side effect of 131-I-MIBG administration is thyroid dysfunction, relatively few data are reported about this issue. METHODS: A series of 14 long term surviving patients with neuroblastoma who had been treated with 131-I-MIBG courses ranging from 2.5 to 5.5 gigabecquerels after surgical and conventional pharmacologic therapy is reported. RESULTS: Twelve patients developed primary hypothyroidism that was clinically overt in 8 patients and compensated in 4 patients within 6-12 months of completion of 131-I-MIBG administration. Only in two patients was thyroid function spared. Significant correlations between the cumulative dose of 131-I-MIBG and the degree of thyroid failure were not found. CONCLUSIONS: Primary hypothyroidism appears to be a common side effect in children with neuroblastoma treated with 131-I-MIBG. This finding suggests that methods to preserve thyroid function other than oral administration of iodide should be sought.

First line targeted radiotherapy, a new concept in the treatment of advanced stage neuroblastoma.

33 previously untreated advanced stage neuroblastoma patients were treated with [131I]meta-iodobenzylguanidine (MIBG). The number of treatments varied between 2 and 7 per patient (mean 3). Toxicity was seldom severe. Only thrombocytopenia WHO-grade 4 was noticed. Response was documented before surgery for the primary tumour was performed. There was one complete response (CR), 18 partial responses (PR), 11 had stable disease (SD) and 3 had progressive disease (PD). After MIBG therapy and surgery, 12 of 33 patients achieved a CR. This approach is feasible, comparable to multidrug chemotherapy in efficacy and less toxic. Long term results are not known yet.

A new approach in the treatment of stage IV neuroblastoma using a combination of [131I]meta-iodobenzylguanidine (MIBG) and cisplatin.

The outlook for disseminated neuroblastoma (NB) continues to be dismal. NB is a radiosensitive tumour. Owing to its high concentration in NB lesions, [131I]meta-iodobenzylguanidine [131I]MIBG has the potential for specifically delivering very large radiation doses to the malignant cells. Encouraging results have been reported with [131I]MIBG used alone in patients resistant to conventional therapy and at diagnosis. We report the first attempt to explore the integration of this new treatment modality with chemotherapy. Among the drugs effective in NB, cisplatin was chosen because of its high degree of activity against NB, its mild haematological toxicity and the known synergism between cisplatin and radiation. 4 patients, 3 with relapsed, heavily pre-treated, progressive stage IV NB, and 1 with stage IV NB at diagnosis, all with a good [131I]MIBG uptake, were investigated with combined therapy (CO-TH). Two complete remissions and one partial remission were observed in these patients 4-6 weeks following only a single course of both cisplatin and [131I]MIBG at "standard" dosage. The only toxicity was haematological, which was significant and relatively long-lasting, but was not associated with any serious infections or bleeding tendency. The general condition of these patients during the entire study period was excellent. The fourth patient, investigated at diagnosis with a modified less intensive treatment, obtained a partial remission with mild haematological toxicity. During the subsequent courses of intensive multidrug chemotherapy, this patient showed haematological toxicity comparable with that experienced by patients treated with an identical drug combination, but without previous treatment with CO-TH. The provisional conclusion of this ongoing study is that this new form of CO-TH appears most effective in obtaining a rapid and excellent response in heavily pretreated relapsed patients with progressive disease, and should be further investigated in earlier stages of the disease.

131I-metaiodobenzylguanidine therapy for malignant pheochromocytoma.

131I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patient had no symptoms before 131I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 week to 1 month after 131I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from 131I-MIBG therapy. Thus, 131I-MIBG appears to be useful for the palliation of malignant pheochromocytoma.

Preliminary report of an ongoing phase I/II dose range, safety and efficacy study of iodine-123-phenylpentadecanoic acid for the identification of viable myocardium.

An agent that can accurately and cost-effectively identify viable myocardium is needed to select the patients most likely to benefit from myocardial revascularization. Iodine-123-phenylpentadecanoic acid (IPPA) is a synthetic radiolabeled fatty acid that has shown promise in evaluating patients with coronary artery disease (CAD). IPPA has unique metabolic properties that may make it superior to other single-photon agents used for this task. A Phase I/II study is underway to evaluate safety, dose range and efficacy of IPPA in assessing viability and predicting functional recovery after revascularization. Patients between the ages of 21 and 75 with angiographically documented CAD, who were being referred for coronary revascularization, were recruited. The patients were randomized to receive 2, 4 or 6 mCi of IPPA and then underwent sequential SPECT imaging at 4, 12, 20, 28 and 36 min after injection. Radionuclide ventriculography and perfusion imaging were performed before and again 8 wk after revascularization. Myocardial metabolic activity of IPPA was analyzed and compared to the preinjection and postejection fractions. There were no significant adverse effects from the administration of IPPA. Image quality was dose-dependent; the 2-mCi dose was not consistently acceptable for quantitative analysis. These preliminary data show that IPPA is safe and can produce myocardial images of good quality when 4 mCi or more are used. Early results are encouraging but more experience will be needed to define the role of IPPA in identifying myocardial viability.

Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine.

We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131I-MIBG (4.9-8.1 GBq or 132-220 mCi) and ten were given 125I-MIBG (8.3-30.0 GBq or 224-809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131I-MIBG; GBq/kg of body weight; and GBq/m2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131I-MIBG, the highest correlation was obtained between cGy and the log10-transformed platelet ratio (r = -0.86), but comparison of GBq/m2 and the platelet nadir (r = -0.76) or the platelet ratio (r = -0.74) or the log10 transformed platelet ratio (r = -0.73) gave comparable and statistically significant results. For treatments with 125I-MIBG, significant correlations were obtained between GBq/m2 and the platelet ratio (r = -0.81) or GBq/kg and the log10-transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131I-MIBG was 2.6 times more potent than 125I-MIBG in causing a platelet ratio of 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Salvage treatment after r-interferon alpha-2a in advanced neuroendocrine tumors.

The use of inteferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN alpha-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIGB uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m2 intravenously days 1, 2, 3 and epirubicin 75 mg/m2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective.

Phase I/II study of iodine 131 metaiodobenzylguanidine in chemoresistant neuroblastoma: a United Kingdom Children's Cancer Study Group investigation.

PURPOSE: The goal of this study was to evaluate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in metastatic neuroblastoma. PATIENTS AND METHODS: A multicenter phase I study of 131I mIBG has been undertaken by the United Kingdom Children's Cancer Study Group (UKCCSG) in children with advanced chemoresistant neuroblastoma. Activity prescription was based on a prescribed whole-body radiation dose, which was established for individual patients by performing an initial tracer investigation with 75 MBq of 131I mIBG. An activity was derived from this pharmacokinetic study that would deliver an initial whole-body-absorbed radiation dose of 1 Gy. Subsequent dose escalations were based on observed toxicity. RESULTS: Twenty-five patients, aged 1 to 10 years, were treated with prescribed whole-body dose levels of 1.0 Gy (n = 2), 2.0 Gy (n = 13), and 2.5 Gy (n = 10). This necessitated administration of 2.4 to 12.1 GBq of activity. Hematologic, hepatic, kidney, and adrenal toxicity were observed, with bone marrow suppression being the principal dose-limiting toxicity. Bone marrow toxicity increased with prescribed whole-body-absorbed radiation dose, with 80% of patients developing grade 3 or 4 thrombocytopenia at a prescribed whole-body radiation dose of 2.5 Gy. Objective evidence of tumor response was seen in soft tissue (primary or nodal disease), bone, and bone marrow, with an overall response rate of 33% (partial response, n = 8; static disease, n = 9; progressive disease, n = 7). CONCLUSIONS: This study has established an effective method of activity prescription that predicts subsequent toxicity, with the maximally tolerated dose being sufficient activity to deliver a whole-body-absorbed radiation dose of 2.5 Gy. The objective response rate is comparable to other single agents in chemoresistant neuroblastoma and suggests that 131I mIBG may be a useful method for targeting radiotherapy in metastatic neuroblastoma.