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.     

Therapy of pheochromocytoma with [131I]metaiodobenzylguanidine.

Fourteen patients with chromaffin tumors were treated with [131]metaiodobenzylguanidine (131I-MIBG); 13 of them suffered from malignant and one from benign pheochromocytoma. In all patients clinical symptoms were improved. In some of these patients tumor shrinkage was observed. In one patient surgery of all tumor tissue was made possible by 131I-MIBG treatment. As shown in one patient, close follow-up is necessary in any case because remnant tumor tissue may start growing again after a long period of rest.     

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.     

Autoradiographic localization of [125I]-C-ANP compared to [125I]-ANP in rat tissue.

Whole-body autoradiography demonstrated the different distribution of [125I]-C-ANP and [125I]-ANP to rat tissues. Highest enrichment of radioactivity of both labelled peptides was found in the kidney. In some organs we found remarkable differences between [125I]-ANP and [125I]-C-ANP. In the kidney cortex, especially in the glomeruli, as well as in the endocardium, the zona glomerulosa and the medulla of the adrenal gland, where high levels of radioactivity after [125I]-ANP administration were detected, no or just few radioactivity was found after administration of [125I]-C-ANP. On the other hand in the kidney papilla and the outer subcortical medulla, characteristic blackening was found after [125I]-C-ANP administration. Those differences might be important for the understanding of pharmacological actions of ANP analogues.     

Results of [131I]metaiodobenzylguanidine treatment in metastatic malignant phaeochromocytoma.

The results obtained with [131I]metaiodobenzylguanidine (131I-MIBG) treatment in 6 patients affected by metastatic phaeochromocytoma are reported. Single doses of 3.7-7.4 GBq were given, in 1-6 courses, up to cumulative doses of 5.4-37.8 GBq. Objective responses were observed in 5 patients (2 tumour shrinkages, even if small; 5 lowering of blood pressure), which were only temporary in 3 patients and stable in 2. Complete disappearance of pain was obtained in 2/2 patients. No adverse side-effects were observed. The problem of treatment strategy in situations of stable disease deserves further study.     

Role of [131I]metaiodobenzylguanidine therapy in medullary thyroid carcinoma.

In recent years several radiopharmaceuticals have become available, offering new possibilities for the diagnosis and therapy of medullary thyroid carcinoma (MTC). For the diagnosis and follow-up 201TI-chloride and 99mTc(V)-DMSA are the tracers of choice. Imaging with [131I]metaiodobenzylguanidine (131I-MIBG) and 131I-anti-CEA or anti-calcitonin antibodies or fragments is less sensitive but very specific. These tracers can be used to evaluate their potential therapeutic use. Cumulative reported data on the diagnostic use of 131I-MIBG in 178 MTC patients indicate that overall 34.5% of medullary cancers concentrate MIBG. At The Netherlands Cancer Institute 131I-MIBG scintigraphy was positive in 8 of 23 patients with MTC. Four of these patients have received therapeutic amounts of 131I-MIBG, resulting in 1 partial remission and meaningful palliation in 3 patients with metastatic MTC. It is concluded that, although the preliminary experience suggests that the objective response of MTC to 131I-MIBG therapy is limited, the palliation provided to these patients, for whom there is little other treatment, may be very meaningful.     

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.     

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.     

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.