Results of [131I]metaiodobenzylguanidine treatment in metastatic carcinoid.

The results obtained with [131I]metaiodobenzylguanidine (131I-MIBG) treatment in 6 patients affected by metastatic carcinoid are reported. 131I-MIBG was given in single doses of 3.7-8.0 GBq, reaching a maximum cumulative dose of 29.5 GBq in 4 courses. Objective responses were not observed, but in 4 cases an apparent stabilisation of the disease for more than 1 year was obtained. A subjective response regarding the carcinoid syndrome was observed in 4 cases. No response was seen in 2 cases. No adverse side-effects of any importance were observed, usually being prevented by a mild medication.     

The role of [131I]metaiodobenzylguanidine in the treatment of medullary thyroid carcinoma: results in five cases.

Therapeutic doses of [131I]metaiodobenzylguanidine (131I-MIBG) were administered to 5 patients, 3 men and 2 women aged from 33 to 66 years, with proven medullary thyroid carcinoma (one "intermediate" papillary/medullary tumor). The treatment procedure consisted of single doses (3.7-8.5 GBq) of 131I-MIBG given by slow i.v. infusion at 2-8 month intervals. In two advanced-stage patients the treatment played an important palliative role, ranging from an objective response (substantial, but not complete, regression of the tumor) to pain relief which was significant for these patients. In three other cases with residual/recurrent tumor, 131I-MIBG complemented conventional treatment in the attempt to effect a cure which actually was achieved in one case. The only side-effect observed was a transient, mild hematologic toxicity in some cases.     

131I]metaiodobenzylguanidine treatment of malignant pheochromocytoma: experience of the Rome group.

Five cases of malignant pheochromocytoma (3 men and 2 women, aged 26-43 years) were treated with [131I]metaiodobenzylguanidine (131I-MIBG). One patient had a voluminous adrenal tumor and multiple distant metastases; two patients had a recurrent tumor; two others a post-surgical residual tumor. The therapeutic procedure essentially consisted of single doses (2.6-7.4 GBq) of 131I-MIBG administered by slow i.v. infusion, given in several therapeutic courses at 1-5 month intervals. The treatment resulted in a complete response in one case with residual tumor and in a partial response in the case with disseminated disease. Two cases showed stabilization of the disease, whereas therapy was ineffective in the fifth case. Nevertheless, pain relief was observed in this patient. The treatment had a very low toxicity and was well tolerated by all patients.     

131I]metaiodobenzylguanidine therapy in advanced neuroblastoma.

Forty-two children with advanced neuroblastoma who either failed with first-line therapy or relapsed after achieving a complete remission, were considered for treatment with [131I]metaiodobenzylguanidine (131I-MIBG). We subdivided 42 cases into 5 groups, in accordance with the stage of disease at diagnosis, response to first-line therapy and relapse. A total of 99 courses of 131I-MIBG were administered with doses ranging from 2.8 to 6.0 GBq. One child received six courses, 3 four courses, 18 three courses, 6 two courses and 15 one course of 131I-MIBG. The total delivered dose in single measurable lesions ranged from 286 to 1691 cGy with an uptake factor ranging from 3% to 10%. We obtained a major response in primary tumors, and a long-term response was observed in 5 cases, lasting more than 2 years without further chemotherapy.     

The use of [131I]metaiodobenzylguanidine in the treatment of neuroblastoma after conventional therapy.

Eleven cases of neuroblastoma (10 males and 1 female; 9 aged 1-13 years, and two aged 17 and 38 years, respectively) ten of which were refractory to chemotherapy, were submitted to treatment with [131I]metaiodobenzylguanidine (131I-MIBG). The therapeutic procedure consisted essentially of single doses (2.6-9.5 GBq) of 131I-MIBG mostly split into two parts, administered by slow i.v. infusion and given in several therapeutic courses, usually at 1-2 month intervals. The treatment resulted in: 1 complete response, 1 partial response, 1 minor response, 4 stabilized diseases and 2 progressive diseases (two patients were not evaluable due to rapid progression of the disease). Pain relief was observed in all cases and particularly in four patients who suffered severe tumor pain. The major side-effects recorded were: hypertensive crises over a 6-day period in one case, fever lasting a few days in another and bone marrow depression in two intensively pretreated patients. A slight hematologic toxicity was observed, however, in almost all cases.     

Long-term results of [131I]metaiodobenzylguanidine treatment of refractory advanced neuroblastoma.

Fourteen patients with advanced neuroblastoma, which was unresponsive to or had relapsed despite conventional therapy, were entered into a phase I/II trial of [131I]metaiodobenzylguanidine (131I-MIBG). Doses ranged from 1.85-8.14 GBq each (50-220 mCi), with cumulative doses of 1.85-24.20 GBq (50-654 mCi) in one to three doses. Side effects included mild nausea and vomiting and moderate myelosuppression which occurred in nine patients. Subjective responses occurred in five patients. Four patients had objective responses (one partial, two minor and one mixed). Two of these patients remain alive 80 and 60 months after beginning 131I-MIBG therapy. Comparison of the 131I-MIBG treated patients with 11 carefully matched control patients treated with an advanced current chemotherapy protocol (CCG 8605) was performed by means of Kaplan-Meier life table analysis. The 14% four-year survival with 131I-MIBG compared favorably with the 6% achieved by salvage chemotherapy. We thus believe 131I-MIBG may have a role in the management of neuroblastoma.     

Experience with palliative [131I]metaiodobenzylguanidine therapy in advanced neuroblastoma.

Our experience with palliative [131I]metabenzylguanidine (131I-MIBG) therapy in 7 patients (6 children and 1 adult) affected by advanced neuroblastoma is reported. All patients (classified as IV stage) showed a progression following initial intensive therapy, including chemotherapy and, in some cases, hemi-body irradiation and surgery for their primary tumor. 131I-MIBG activity ranged for a single course between 2.77 GBq to 5.55 GBq on the basis of age, intensity of uptake, and the hematological assessment. Four patients received only one course of therapy due to progressive disease (2), early death (1) or persistent thrombocytopenia unrelated to 131I-MIBG therapy (1). Two patients received two courses and showed a partial response lasting 4 months and stable disease lasting 3 months respectively. Therapy was thereafter discontinued due to progression. One patient received 4 courses of therapy (cumulative activity = 19.61 GBq) in 5 months. A partial response for 9 months in the bone metastases was documented, but the therapy was discontinued due to persistent thrombocytopenia (58,000 plts/microL) lasting 4 months. Thrombocytopenia was the major side-effect, occurring in 5/7 patients over 8 courses of therapy for a mean period of 37 days (7-120 d). Thus, in our experience thrombocytopenia is the major factor limiting the therapeutic effect of 131I-MIBG therapy in palliative treatment.     

Treatment of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: a French multicenter study.

Six Medical Centers in France were involved in a prospective study evaluating the efficacy of [131I]metaiodobenzylguanidine (131I-MIBG) in the treatment of malignant pheochromocytoma. Fifteen patients aged from 28 to 75 years bearing tumor sites demonstrating a good MIBG uptake were included in this study. Catecholamines were elevated in 13/14 cases, VMA in 9/14 and metanephrines in 13/14. Two to 11 therapeutic activities of 131I-MIBG were administered, with a mean number of therapeutic doses per patient of 4 and a mean single activity of 4.7 GBq (range 2.9 to 9.25 GBq). Seven patients were alive, and seven patients died 6 to 29 months after their first MIBG administration (mean follow-up of 36 months); 1 patient was lost to follow-up. Two patients had a partial tumor response only, 4 had a hormonal response only, and 3 had both a partial tumor response and a hormonal response (complete in 2 cases). Six patients did not respond to the treatment, 4 of them died. Of the 9 responding patients, 4 relapsed, 3 of whom died subsequently. Haematological toxicity was always transient and mild, except in 1 case.     

Role of [131I]metaiodobenzylguanidine therapy in carcinoids.

From cumulative reported data the sensitivity of [131I]metaiodobenzylguanidine (131I-MIBG) scintigraphy of carcinoids appears to be greater than 60%; at our Institute 131I-MIBG scintigrams were positive in 51 of 70 patients with metastatic carcinoid. Twenty patients with symptomatic, metastatic disease have received 7.4 GBq doses of 131I-MIBG for palliation. Most of these patients had multiple large metastases showing no response to other therapies. No objective response (greater than 50% tumor volume reduction) was ever observed; however, 13 patients were relieved of symptoms, such as flushes, diarrhea, anorexia and pain. Palliation in some of these patients was meaningful and long lasting. Possible explanations for a palliative effect in the absence of objective remission are discussed. Treatment with escalating doses of stable MIBG (up to 80 mg) in 9 patients does not support the hypothesis that the palliation is due to a purely pharmacological effect. Palliation might be explained by the observation that carcinoid liver metastases may present both as hot and cold lesions; 131I-MIBG therapy will thus target exclusively at metabolically active metastases, which are responsible for the patient's symptoms.     

131I]metaiodobenzylguanidine treatment of a malignant paraganglioma.

The bone metastases of a malignant, non-secreting paraganglioma were treated with [131I]metaiodobenzylguanidine (131I-MIBG) over a 10-year period. Initial treatment (131I-MIBG: 9.6 GBq) resulted in a decrease in the number of bone metastases from 16 to 2. At three years, a relapse with primary tumor regrowth and liver metastasis was again treated with 131I-MIBG (22.2 GBq). A decrease in the number of bone metastases and MIBG uptake was again observed.     

Preliminary results of [131I]metaiodobenzylguanidine treatment in metastatic carcinoid tumors.

The successful use of [131I]metaiodobenzylguanidine (131I-MIBG) in the scintigraphic localisation and treatment of several tumors deriving from neuroectoderm has led us to its application in metastatic carcinoid tumors. We selected five patients (two men and three women; age range 53-79 years) who showed progression of the disease with severe related symptoms, poor response to traditional therapy and a good uptake of 131I-MIBG in neoplastic tissue. A cumulative radioactivity of 3.7-22.2 GBq was given. All patients had a clear subjective improvement with a better quality of life for a period of 2-36 months, sometimes accompanied by decreased 5-hydroxyindoleacetic acid urinary excretion. Results concerning objective remission of the disease were unsatisfactory. No remarkable early or late side-effect was noted. We believe 131I-MIBG is useful for symptomatic treatment of metastatic carcinoid in seriously ill patients too. Different treatment schedule and recruitment of patients with less advanced disease could make pathological remission a possible goal.     

131I]metaiodobenzylguanidine therapy in medullary thyroid cancer: Guy's Hospital experience.

[131I]Metaiodobenzylguanidine (131I-MIBG) was utilized in the therapy of seven patients with medullary thyroid cancer. Treatment doses ranged from 3.7 to 11 GBq, for upto four total treatments. Six of the seven patients treated showed some response to treatment (from transient partial response to symptom palliation). Treatment was tolerated well in all patients, with minimal side-effects and no signs of hematologic radiotoxicity. These encouraging results emphasize the potential of 131I-MIBG as a form of targetted radiometabolic therapy in patients with medullary thyroid cancer.     

131I]metaiodobenzylguanidine and high-dose chemotherapy with bone marrow rescue in advanced neuroblastoma.

High-dose chemotherapy (HDT) and autologous bone marrow rescue (ABMR) is routinely used as consolidation treatment in advanced neuroblastoma. This study is presently examining the efficacy and toxicity of combined [131I]metaiodobenzylguanidine (131I-MIBG) therapy with HDT and ABMR. Five children (4 male, 1 female), median age of 8 years (range 4-11 years) were treated, 3 at relapse and 2 after initial chemotherapy. A single infusion of 131I-MIBG (median activity 11.1 GBq, range 7.4-11.2 GBq) was followed by HDT and ABMR 14-32 days later. High-dose chemotherapy consisted of carboplatin and melphalan in 4 patients, and vincristine, etoposide, carboplatin and melphalan in 1. One patient developed a septicaemia and died, and another failed to engraft; both had extensive bone marrow infiltration at the time of 131I-MIBG therapy. The combined therapy was well tolerated by the three other patients. Two children have relapsed and died (including one who failed to engraft), and 2 are alive 17 and 41 months after ABMR. In the absence of extensive bone marrow metastases, combined therapy offers potential as a means of consolidating treatment in advanced neuroblastoma.     

甲状腺根治术后不同剂量131I清甲治疗对分化型甲状腺癌患者唾液流率、骨代谢和生活质量的影响

目的:探讨甲状腺根治术后不同剂量131I清甲治疗对分化型甲状腺癌患者唾液流率、骨代谢和生活质量的影响。方法:选取2018年1月~2020年1月期间我院诊治的分化型甲状腺癌患者141例,根据随机数字表法分为低剂量组[治疗剂量为1.1~3.7GBq(30~100 mci)]、中剂量组[治疗剂量为3.7~5.5GBq(100~150 mci)]、高剂量组[治疗剂量为5.5~7.4GBq(150~200 mci)],各47例。对比三组患者唾液流率、骨代谢、生活质量、腮腺和颌下腺的摄取参数(UR)和排泌参数(ER)。结果:高剂量组、中剂量组腮腺、颌下腺的左侧UR、右侧UR、左侧ER、右侧ER均低于低剂量组,且高剂量组低于中剂量组(P<0.05)。三组治疗后静态唾液流率(UWSFR)、动态唾液流率(SWSFR)均较治疗前下降(P<0.05),高剂量组、中剂量组治疗后UWSFR、SWSFR低于低剂量组,且高剂量组低于中剂量组(P<0.05)。低剂量组、中剂量组的优良率高于高剂量组,且中剂量组高于低剂量组(P<0.05)。三组治疗前后、组间总Ⅰ型胶原氨基端前肽(PINP)、β-胶原降解产物(β-CTX)、骨密度(BMD)对比,差异均无统计学意义(P>0.05)。结论:不同剂量131I清甲治疗对分化型甲状腺癌患者的骨代谢无明显影响,但不同剂量131I清甲治疗均会影响患者唾液腺功能及生活质量,其中高剂量131I清甲对患者的影响最为显著。     

Evaluation of equivalent body burden in the thyroid for the people of Poland on results of 131I absorption after the disaster in Czernobyl. Determination of thyroid blockade with potassium iodide]

An assessment of effectiveness of the administering of single dose of stable iodine in Poland on the reduction of 131I doses in thyroid has been performed. 5-compartment model of metabolism of iodine developed by Johnson has been used to evaluate predicted levels of stable iodine and 131I content in thyroid and commitment dose equivalent H50 for different doses of stable iodine and various age and sex group population. The measured values of 131I concentration in air and in milk and standard values for milk and food consumption and inhalation rate as well as metabolic parameters were used. Theoretical calculations showed that administering of stable iodine on 1986-04-28, 1986-04-29, 1986-04-30 and 1986-05-01 could have reduced committed dose equivalent H50 form ingestion with inhalation pathway by about 44%, 40%, 26%, 12% respectively. On the basis of measured 131I activity in the thyroid for inhabitants from different districts in Poland (1400 measurement) committed dose equivalents were determined and analysis of radiation hazard from 131I were performed. In the most contaminated regions of Poland average H50 doses for children 1-5 and 5-10 years old are close to 50 mSv (permissible level for population) and maximal doses exceed this limit four times. These maximal doses occurred for about from 5% inhabitants from these area. In the moderate and low contaminated regions of Poland the average doses are fivefold and tenfold less respectively.     

Results of [131I]metaiodobenzylguanidine therapy administered to three patients with malignant pheochromocytoma.

Three patients with malignant pheochromocytoma were treated with [131I]metaiodobenzylguanidine (131I-MIBG). In two patients with widespread metastatic disease, the effect of treatment was palliative and of short duration. In the third case, with only residual tumor and no metastases, the treatment was effective after 22 GBq of 131I-MIBG.     

Efficacy and safety of [131I]metaiodobenzylguanidine therapy for patients with refractory neuroblastoma.

Metaiodobenzylguanidine (MIBG) is a guanethidine derivative that is selectively concentrated in sympathetic nervous tissue. MIBG labeled with 123I or 131I has proven to be a specific and sensitive tool for detection of primary and metastatic pheochromocytoma and neuroblastoma. Eleven patients, with refractory stage IV neuroblastoma were treated with a total of 23 courses of 131I-MIBG, 100-400 mCi/m2/course. Total activity administered per course ranged from 90-550 mCi; maximum cumulative radioactivity per patient was 1356 mCi. The 131I-MIBG was given as a 2 hour infusion. Total body dose was calculated from whole body activity measurements, ranging from 73-250 cGy. The main toxicity was thrombocytopenia, with platelet nadirs to less than 25,000/microL in 5/23 courses (5 patients), all occurring in patients with greater than 25% replacement by tumor in the bone marrow. Neutropenia to a nadir of less than 500/microL was seen in only 2 patients, both with greater than 50% bone marrow replacement after 2 and 4 courses of 131I-MIBG, respectively. Tumor doses were calculated in patients with an evaluable measurable lesion, and ranged from 312-6329 cGy per course. Two of the eleven patients had partial responses, with one long-term survivor with stage IV neuroblastoma with no evidence of active disease now 4 years off treatment. Two other patients survive with stable disease after 3 treatments, at 3+ and 5+ months. Seven patients died with progressive disease. This study shows that treatment with 131I-MIBG is safe and can be effective in refractory neuroblastoma, particularly in patients who do not have extensive bone and bone marrow involvement.     

131I]metaiodobenzylguanidine therapy in 20 patients with malignant pheochromocytoma.

Twenty patients, 16 male and 4 female (aged 11-76 years), with metastatic pheochromocytoma were treated in our Institution between 1985 and 1990. Metastases occurred in all patients: at presentation in 11 patients, with a 10 to 30 month delay in 7 patients, and 9 and 28 years later respectively in 2 patients. Catecholamines hyperproduction was present in all patients. Metaiodobenzylguanidine (MIBG) uptake was found in 16 patients after a diagnostic dose and only after a therapeutic dose in 1 patient. Surgery was performed on primary tumor (18 patients) and on distant metastases (10 patients). 131I-MIBG therapy was performed in 11 patients, 9 of whom were evaluable. The cumulative activity ranged from 3.7 to 26.3 GBq (100 to 711 mCi) in 1 to 6 courses. We observed symptomatic improvement (5 patients) and partial tumor response in 2 patients, which lasted for 28 and 9 months respectively, terminating with a rapidly progressing disease involving the bone marrow. Stabilisation was observed in 3 patients. Moderate myelosuppression occurred in 4 patients. Fifteen patients died with a median survival of 16 months (range 3-60). Response to therapy was poor and further evaluation of the presently available therapeutic approaches is needed.     

90Y-DOTA-D-Phe1-Try3-octreotide in therapy of neuroendocrine malignancies

Somatostatin receptors type 2 (sst(2)) are expressed in high concentration on numerous neudoendocrine tumors. The successful use of radiolabeled somatostatin analogs in imaging promoted further studies in utilizing them in radiopeptide therapy. The somatostatin analog [(90)Y-DOTA-D-Phe(1)-Try3]octreotide (DOTATOC) (DOTA: 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) possesses favorable characteristic for its therapeutic use; shows high affinity for sst(2), moderately high affinity for sst(5), and intermediate affinity for sst(3); high hydrophilicity; stable and facile labeling with (111) In and (90) Y. In this article we report our experience with (90)Y-DOTATOC in neuroendocrine tumors. Eighty-seven patients with neuroendocrine tumors were treated with a cumulated activity ranging from 7.4 to 20.2 GBq. Most patients responded with stabilization of disease (48%); however, objective responses were observed in 28% of patients (5% complete response). No major acute reactions were observed up to the activity of 5.55 GBq per cycle. The dose limiting was bone marrow toxicity and the maximal tolerated dose was defined as 5.18 GBq.     

Dependency of the remnant 131I-NaI biokinetics on the administered activity in patients with differentiated thyroid cancer

PurposeTo study the dependency of the effective half-life on the administered activity and the correlation between the time-integrated activity and the remnant uptake at 2d and 7d in patients treated for DTC with 1.11 GBq, 3.7 GBq or 5.55 GBq of ¹³¹I-NaI.MethodsNinety-two patients undergoing total thyroidectomy and lymph node removal were included. If cancer had not spread to lymph nodes, patients received 1.11 GBq of ¹³¹I-NaI when the lesion maximal diameter was smaller than 4 cm, and 3.7 GBq for bigger sizes. If cancer had spread to lymph nodes patients received 5.55 GBq. There were 30, 49 and 13 patients respectively treated with 1.11 GBq(Group 1), 3.7 GBq(Group 2) and 5.55 GBq(Group 3). Two SPECT/CT scans were performed at 2d and 7d after radioiodine administration for each patient to determine the thyroid remnant activities and effective half-lives of the radioiodine.ResultsStatistical analysis showed significant differences (p < 0.05) in the effective half-life among patients treated with 1.11 GBq, 3.7 GBq and 5.55 GBq. A high positive correlation (ρ > 0.95) was found between the time-integrated activity and the remnant activity at 2d for the three groups of patients.ConclusionsThere were significant differences in the effective half-life of the radioiodine in remnants of patients treated with activities of 1.11 GBq, 3.7 GBq or 5.55 GBq. The high positive linear correlation found between the time-integrated activity and the remnant activity at 2d for the three groups of patients indicate that the time-integrated activity could be estimated from one time-point.