131I]metaiodobenzylguanidine in neuroblastoma patients at diagnosis.

Treatment of resistant neuroblastoma with high dosage [131I]metaiodobenzylguanidine (131I-MIBG) appears effective since encouraging results have been obtained so far even in patients with very advanced, intensively pre-treated disease. We have already reported a stage III NB patient treated at diagnosis, who is at present in complete remission with a 4-year follow-up. To further explore the potential role of this new drug in untreated patients, we administered radionuclide to two children with stage III neuroblastoma. Both cases received 131I-MIBG at relatively low doses, and showed a significant reduction of the tumor mass and, interestingly enough, no evidence of 131I-MIBG uptake of a tracer dose in the remaining tumor. Particularly in case 1, the permanence and subsequent progression of the part of the tumor mass without 131I-MIBG uptake, after therapeutic doses of 131I-MIBG which apparently destroyed the 131I-MIBG-positive cell population, clearly suggest heterogeneity at diagnosis, with a dual neuroblastoma cell population, one with 131I-MIBG uptake and the other without. Aside from the biological implications of the heterogeneous MIBG uptake in neuroblastoma at diagnosis, our findings suggest that in stage III neuroblastoma patients even a relatively small dose of 131I-MIBG administered at diagnosis is sufficient to either completely destroy the primary tumor, as reported by our group, or to destroy that part of the tumor which shows 131I-MIBG uptake (as in the present cases), without any significant hematologic toxicity. Furthermore, a single course of 131I-MIBG at the dosage employed here does not appear to jeopardize the subsequent use of chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro pharmacology of metaiodobenzylguanidine uptake, storage and release in human neuroblastoma cells.

Four human neuroblastoma (NB) cell lines (LAN-5, SK-N-BE(2)C, GI-LI-N, and GI-CA-N) have been investigated for their ability to take up and store [125I]metaiodobenzylguanidine (125I-MIBG) in vitro. Only SK-N-BE(2)C and LAN-5 cells were able to specifically take up MIBG, with the former cell line showing a more efficient retention of the radiotracer. 125I-MIBG incorporation in both cell lines was inhibited by norepinephrine, desipramine, ouabain and energy depletion. Thus, all the major criteria for specific (type 1) uptake were fulfilled. Conversely, GI-LI-N and GI-CA-N cells did not show any specific uptake. Pharmacological manipulations aimed at defining the intracellular site(s) of 125I-MIBG storage clearly showed that the radiotracer is not accumulated in the reserpine-sensitive neurosecretory granules and vesicles in NB cells, contrary to what has been observed in a chromaffin derived tumor cell line (PC12). Our study provides new and suitable models to investigate in vitro the molecular and cellular pharmacology of MIBG in NB cells.     

Hypoxia-induced erythropoietin expression in human neuroblastoma requires a methylation free HIF-1 binding site

The glycoprotein hormone Erythropoietin (EPO) stimulates red cell production and maturation. EPO is produced by the kidneys and the fetal liver in response to hypoxia (HOX). Recently, EPO expression has also been observed in the central nervous system where it may be neuroprotective. It remained unclear, however, whether EPO is expressed in the peripheral nervous system and, if so, whether a neuronal phenotype is required for its regulation. Herein, we report that EPO expression was induced by HOX and a HOX mimetic in two cell lines derived from neuroblastoma (NB), a tumor of the peripheral nervous system. Both cell lines with inducible EPO expression, SH-SY5Y and Kelly cells, expressed typical neuronal markers like neuropeptide Y (NPY), growth-associated protein-43 (GAP-43), and neuron-specific enolase (ENO). NB cells with a more epithelial phenotype like SH-SHEP and LAN-5 did not show HOX inducible EPO gene regulation. Still, oxygen sensing and up-regulation of hypoxia-inducible factor-1 (HIF-1) were intact in all cell lines. We found that CpG methylation of the HIF binding site (HBS) in the EPO gene 3' enhancer was only present in the SH-SHEP and LAN-5 cells but not in SH-SY5Y and Kelly cells with regulated EPO expression. The addition of recombinant EPO to all NB cells, both under normoxic and hypoxic conditions, had no effect on cell proliferation. We conclude that the ability to respond to HOX with an increase in EPO expression in human NB may depend on CpG methylation and the differentiation status of these embryonic tumor cells but does not affect the proliferative characteristics of the cells.     

The Epithelial Phenotype of Human Neuroblastoma Cells Expresses Bradykinin, Endothelin, and Angiotensin II Receptors That Stimulate Phosphoinositide Hydrolysis

The neuroblastoma line SK-N-SH consists of distinct and interconverting cell types, which include a neuroblast phenotype (SH-SY5Y), an epithelial phenotype (SH-EP), and an intermediate cell type (SH-IN). In SH-SY5Y cells, only muscarinic receptor activation produced stimulation of phosphoinositide turnover, whereas in SH-EP cells, where muscarinic receptors are not present, the peptides bradykinin, endothelin, and angiotensin II stimulated phosphoinositide hydrolysis with EC50 values of 16, 6, and 0.7 nM, respectively, and a rank order of maximal effects of bradykinin greater than endothelin greater than angiotensin II. Fetal calf serum at concentrations between 1 and 10% was also a potent stimulator of phosphoinositide hydrolysis in SH-EP cells but not in SH-SY5Y cells. In the intermediate cell clone, SH-IN, phosphoinositide hydrolysis was stimulated not only by muscarinic receptors, but also by endothelin, bradykinin, and serum, an indication that this cell type harbors all the kinds of receptors that are differentially expressed in the other two cell types. The effects of the three peptides--bradykinin, endothelin, and angiotensin II--on phosphoinositide hydrolysis in SH-EP cells were additive, a result suggesting that the three kinds of receptors may activate distinct transducer proteins and/or phospholipase C subtypes. Pretreatment of intact SH-EP cells with pertussis toxin under conditions sufficient to ADP-ribosylate 90-95% of the endogenous guanine nucleotide regulatory protein substrates did not impair the ability of any of the receptors to stimulate phosphoinositide hydrolysis in any of the cell types. In contrast, short-term exposure to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (1 microM) abolished the stimulation of phosphoinositide hydrolysis mediated by peptide receptors in SH-EP cells and partially inhibited that by muscarinic receptors in SH-SY5Y cells. Prolonged incubation of SH-EP cells with phorbol ester resulted in a recovery of receptor responsiveness, the extent and rate of which were different for each receptor type. In contrast, there was no recovery of responsiveness for muscarinic receptors in SH-SY5Y cells. The pattern of phorbol ester-mediated effects depended on the cell rather than on the receptor type. In fact, muscarinic receptor responsiveness in SH-IN, the intermediate cell type, was desensitized by and recovered from treatment with phorbol esters in a manner more similar to peptide receptors in SH-EP than to muscarinic receptors in SH-SY5Y. These data suggest that the transduction mechanisms by which distinct receptor types are coupled to phosphoinositide hydrolysis in the three cell phenotypes differ in sensitivity to feedback regulation by protein kinase C.     

Uptake of 131I-metaiodobenzylguanidine by 6-23 rat medullary thyroid carcinoma

Uptake of 131iodine-metaiodobenzylguanidine (131I-MIBG) by 6-23 rat medullary thyroid carcinoma (MTC), was studied in vitro and in vivo. In vitro, there was an 8-fold increase in 131I uptake by 6-23 cells when labeled with 131I-MIBG (131I 24 +/- 15 cpm/10(6) cells, 131I-MIBG 196 +/- 9 cpm/10(6) cells). MIBG uptake in vitro was the same at 4 degrees C and 37 degrees C. In contrast, 131I-MIBG uptake by PC-12 rat pheochromocytoma cells were 200 times greater (131I-MIBG 42,412 +/- 6,755 cpm/10(6) cells). 131I-MIBG uptake by rat MTC cells in vitro were of a comparable magnitude to the uptake of 131I-MIBG by rat ileal enterochromaffin cells (RIE-1) and mouse colon cancer cells (MC-26). In vivo, uptake of 131I-MIBG by 6-23 MTC tumor was considerably less than in the normal tissues (muscle, liver, spleen, kidney, adrenal and thyroid). Gamma camera studies of 131I-MIBG uptake by 6-23 MTC tumors growing in Wag-Rij rats were only transiently positive in 1 out of 4 rats studied. We conclude that 131I-MIBG is poorly taken up by rat medullary thyroid carcinoma and is an unpredictable marker for localization of rat MTC.     

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.     

Outcome of [131I]metaiodobenzylguanidine therapy of neuroblastoma: seven years after.

Beginning in 1984 and based on a total of 40 treatments with [131I]metaiodobenzylguanidine (131I-MIBG) in most cases with a follow-up of 5 years or more, it seems to be worthwhile reevaluating our clinical data and draw some final conclusions: We treated 12 children with a neuroblastoma (NB) IV and 3 with a NB III. In no case 131I-MIBG was the primary therapy. The great majority suffered from recurrence. The mean treatment interval after chemotherapy was 6 months (range 0-54). We calculated a median cumulative tumor dose of 77 Gy (range 0-259) in patients with stage III and 30 Gy (range 4-267) in stage IV NB. The tumor half-life time of 131I-MIBG does not significantly differ between stage III (3 days) and IV (2-5 days). Although the median tumor dose of stage III NB exceeded that of stage IV, we found in NB IV a significant tumor remission in 7 out of 12 cases. On the other hand, a slight reduction of tumor size was seen in only 1 case of stage III NB. This indicates a lower radiation sensitivity of stage III NB. Despite this fact, the two patients with stage III NB who presented a sufficient 131I-MIBG-tumor uptake turned to become operable after 131I-MIBG. Stage IV patients improved, too, even if most of them suffered from recurrence with a very poor prognosis: 3 patients of stage IV lived longer than 48-60 month or are still alive. However, no one of this group remitted completely.(ABSTRACT TRUNCATED AT 250 WORDS)     

Retinoic acid enhances VIP receptor expression and responsiveness in human neuroblastoma cell, SH-SY5Y

Retinoic acid (RA) induces partial differentiation of neuroblastoma (NB) cells in vitro. In the human NB line, SH-SY5Y (a neuroblastic subclone of SK-N-SH), RA was previously shown to enhance the stimulatory (PGE1) and inhibitory (opioid) regulation of adenylyl cyclase. Since these cells are also sensitive to cAMP stimulation by vasoactive intestinal peptide (VIP), we have tested the effects of RA on VIP receptor expression and function. Pretreatment of SH-SY5Y cells with 10 microM RA over 6 days dramatically increased VIP receptor number from approximately 3,000 to approximately 70,000 sites per cell and enhanced threefold the cAMP accumulation after external VIP addition, while VIP immunoreactive content in the cells increased 2-3-fold. In the light of the recently proposed autocrine function of VIP in this cell lineage, the strong enhancement of the VIP system may contribute to the differentiation effects of RA.     

131I]metaiodobenzylguanidine therapy in paraganglioma.

Our experience with [131I]metaiodobenzylguanidine (131I-MIBG) therapy in a 10 year old boy is reported. At disease onset, in May 1988, this boy presented a large mass in the upper left abdominal quadrant, which was resected with a histopathological diagnosis of extra-adrenal malignant pheochromocytoma (paraganglioma). He subsequently underwent two further surgical resections and chemotherapy. When 131I-MIBG therapy was started, in June 1990, skeletal and abdominal metastases were present. These localizations were revealed by 131I-MIBG scans and confirmed by x-ray examination. At present 6 courses of therapy have been performed with a cumulative activity of 29.6 GBq. Side-effects have been limited to vomiting and mild thrombocytopenia, lasting 2 weeks during the second course of therapy. After 15 months of therapy, a progressive reduction of MIBG uptake, coupled with a stabilization of the lythic lesions, has been observed.     

Increased epidermal growth factor receptor in multidrug-resistant human neuroblastoma cells

Multidrug-resistant human neuroblastoma cell lines obtained by selection with vincristine or actinomycin D from two independent clonal lines, SH-SY5Y and MC-IXC, have 3- to 30-fold more cell surface epidermal growth factor (EGF) receptors than the drug-sensitive parental cells as indicated by EGF binding assays and immunoprecipitation, affinity-labeling, and phosphorylation studies. Reversion to drug sensitivity in one line was accompanied by a return to the parental level of EGF receptor. SH-EP cells, a clone derived from the same neuroblastoma cell line as SH-SY5Y but which displays melanocyte rather than neuronal lineage markers, also express significantly more EGF receptor than SH-SY5Y cells. By nucleic acid hybridization analysis with a molecularly cloned probe, increased receptor level in multidrug-resistant cells was shown to be the result of higher levels of EGF receptor mRNA in drug-resistant than in drug-sensitive cells. The increased steady state amount of specific RNA did not result from amplification of receptor-encoding genes. A small difference was observed in the electrophoretic mobility under denaturing conditions of EGF receptor immunoprecipitated from drug-resistant and drug-sensitive cells. Quantitative and qualitative modulation of the EGF receptor might reflect alterations in the transformation and/or differentiation phenotype of the resistant cells or might result from unknown selective pressures associated with the development of multidrug resistance.     

Damage-induced Bax N-terminal change, translocation to mitochondria and formation of Bax dimers/complexes occur regardless of cell fate.

Sequential steps in the activation of the pro-apoptotic protein Bax are described for cells with different sensitivity to cytotoxins. SH-EP1 and SH-SY5Y human neuroblastoma cells, derived from a single precursor cell line, differed in their sensitivity to taxol but showed the same sensitivity to cisplatin. Both drugs, in both cell lines, induced exposure of a constitutively occluded N-terminal epitope of Bax. This was reversible and occurred before the translocation of cytosolic Bax to mitochondria. The N-terminal change in Bax, its subsequent movement to mitochondria and its dimerization/complex formation were insufficient for commitment to death, occurring in the same proportion of cells that either maintained (SH-SY5Y) or lost (SH-EP1) clonogenic survival after taxol treatment. Suppression of taxol-induced apoptosis occurred upstream of cytochrome c release from mitochondria in SH-SY5Y cells. The data suggest that a further drug damage-induced event occurs after Bax dimerization/complex formation but prior to cytochrome c release. This event was absent in the taxol-resistant cells.     

IGF2 derived from SH-SY5Y neuroblastoma cells induces the osteoclastogenesis of human monocytic precursors

The insulin-like growth factors 2 (IGF2) is a peptide hormone that binds to the insulin-like growth factor 1 receptor (IGF1R) and is abundantly stored in bone. IGF1R is deeply involved in the pathogenesis of many cancers that growth within bone and is also involved in osteoclast biology. Among different cell lines representative of osteolytic tumors, we found a very high expression of IGF2 in SH-SY5Y cells derived from neuroblastoma (NB). We previously showed that NB cells induce an osteolytic process through the Osteoprotegerin/RANKL/RANK and the canonical Wnt pathway system. Here, we hypothesized that NB promotes osteoclastogenesis also via IGF2. First, we demonstrated the presence of IGF1R on the osteoclast basolateral membrane, and we observed a cyclic IGF1R activation along with the differentiation process, also when induced by SH-SY5Y. Moreover, we found that IGF2 mRNA expression in SH-SY5Y cells was further increased when co-cultured with mesenchymal stromal cells, suggesting that IGF2 is important for NB interaction with the bone microenvironment. Finally, the treatment of SH-SY5Y cells with an anti-IGF2 siRNA or the addition of anti-IGF1R molecules impaired NB-induced osteoclastogenesis, even though the chemoattraction of monocytes by NB cells was unaffected. Our findings suggest that in IGF2-producing osteolytic tumors IGF1R is a good candidate for targeted therapies in combination with conventional drugs.     

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.     

Morphologic conversion of a neuroblastoma-derived cell line by E6-mediated p53 degradation.

Neuroblastoma-derived tumor cells, unlike cells from other tumor types, characteristically express a wildtype but cytoplasmically sequestered p53 protein. To ascertain whether the p53 in these cells retained any physiological activity, we inactivated it in SK-N-SH cells, a neuroblastoma-derived cell line, by introducing the human papilloma virus type 16 E6 expression plasmid. Parent SK-N-SH cell cultures are composed of two cell types exhibiting characteristic morphologies designated neuroblastic (N-type) or substrate-adherent fibroblastic (S-type) cells, both of which have been shown to spontaneously transdifferentiate or interconvert. We report here that down-regulation of p53 resulted in conversion of SK-N-SH cells to the substrate-adherent fibroblast-like S-type cells. The morphologic conversion was accompanied by a loss of neurofilament expression, a marker for the neuronal N-type cells, an increase in the expression of vimentin, and a lack of responsiveness to retinoic acid-induced neuronal differentiation. Importantly, we did not observe N-type cells in the E6-transfected cell population, suggesting that they were incapable of transdifferentiating to the N-type morphology. We also tested the ability of these E6-transfected S-type cells to form colonies in soft agar and observed a markedly reduced capacity of these cells to do so when compared with the parent and mutant E6-transfected cells. These results suggest that p53 is required for the maintenance of the neuroblastic tumorigenic phenotype.     

Clinical Use and Utility of Metaiodobenzylguanidine Scintigraphy in Pheochromocytoma Diagnosis

ObjectiveTo examine the indications for metaiodo- benzylguanidine (MIBG) scintigraphy and to assess its performance in localizing pheochromocytoma in the post- computed tomography and magnetic resonance imaging era.MethodsIn this retrospective study, electronic and paper medical records of patients who underwent MIBG scintigraphy at a large academic hospital in Los Angeles, California, between January 1995 and July 2009 were reviewed for indications for MIBG scintigraphy, clinical history, biochemical test results, findings from imaging studies, and pathologic diagnoses. MIBG score was defined as follows: 3 (or intensive uptake) meant MIBG uptake of adrenal gland or other locus was higher than that of the liver; 2 (or moderate uptake) meant uptake was similar to that of the liver; 1 (or borderline uptake) meant uptake was lower than that of liver; and 0 (or negative uptake) meant background signal.ResultsNinety-eight patients underwent MIBG scintigraphy during the study period; the indica- tion was suspected pheochromocytoma in 75 cases. Pheochromocytoma diagnosis was excluded in 48 and con- firmed in 15. The remaining 12 patients had insufficient information in the medical records to render a diagnosis. Among the 63 patients, 47 received ¹³¹I-MIBG and 16 received ¹²³I-MIBG. Sensitivity was 73% and specificity was 69% if any adrenal uptake was considered positive, but increased to 90% if borderline uptake was considered negative. False results were more common in younger patients, but not correlated with biochemical test results. In patients with pheochromocytoma either excluded or con- firmed, the MIBG scintigraphy results were confirmatory in 63%, but misleading in 37%. MIBG scintigraphy results did not provide additional diagnostic value to any case and contributed to pheochromocytoma overdiagnosis and even unnecessary adrenalectomy.ConclusionsMIBG scintigraphy results are either confirmatory or misleading, and this imaging modal- ity is not necessary formost patients in modern practice.(Endocr Pract. 2010;16:398-407)     

Therapeutic use of [131I]metaiodobenzylguanidine in neuroblastoma: a phase II study in 26 patients. "Société Fran?aise d'Oncologie Pédiatrique" and Nuclear Medicine Co-investigators.

Seven French Medical Centers were involved in a cooperative study evaluating [131I]Metaidobenzylguanidine (131I-MIBG) therapy in advanced neuroblastoma. Children (median age 4 years) had initially a stage III (4 patients) or stage IV (22 patients) neuroblastoma. Before MIBG treatment, 14 patients had a primarily refractory disease, 10 patients were relapsing; in 8 cases, autologous bone marrow transplantation had been performed. Tumour sites were in 24 patients: 13/24 local disease, 8/24 bone metastases, and 7 bone marrow involvement. Catecholamines were elevated in 7/24 patients. The median activity of 131I-MIBG per injection ranged from 30 to 108 mCi; the number of injections varied from 1 to 5. We observed 5/10 pain palliations and 10/24 stabilizations of the disease course for 1 to 7 months with no objective volume tumour response. Haematologic toxicity caused a platelet count less than 150,000/microL in 4 patients, less than 100,000 in 1 patient and less than 50,000 in 7 patients.     

A radioiodinated MIBG-octreotate conjugate exhibiting enhanced uptake and retention in SSTR2-expressing tumor cells

Several neuroendocrine tumors are known to express both the somatostatin receptor subtype 2 (SSTR2) and the norepinephrine transporter (NET), and radiopharmaceuticals directed toward both these targets such as MIBG and octreotide derivatives are routinely used in the clinic. To investigate the possibility of targeting both NET and SSTR2 conjointly, a conjugate of radioiodinated MIBG and octreotate was synthesized. Attempts to synthesize the radioiodinated target compound (MIBG-octreotate; [ (131)I] 12a) from a tin precursor were futile; however, it could be accomplished from a bromo precursor by exchange radioiodination in 3-36% ( n = 10) radiochemical yields. The total uptake of [ (131)I] 12a in SK-N-SH human neuroblastoma cells transfected to express SSTR2 (SK-N-SHsst2) was similar to that for [ (125)I]MIBG at all time points (34.9 +/- 2.4% vs 43.8 +/- 1.2% at 4 h; p < 0.05), while it was substantially lower (5.4 +/- 0.3% vs 35.9 +/- 1.2%) in the SH-SY5Y cell line, a subclone of SK-N-SH line that is known to express SSTR2. The NET blocker desipramine reduced the uptake of [ (131)I] 12a only to a small extent, further suggesting a limited role of NET in its binding and accumulation. Uptake of [ (131)I] 12a in SK-N-SHsst2 cells was 8-10-fold higher ( p < 0.05) than that of [ (125)I]I-Gluc-TOCA, an octreotide analogue, at all time points over a 4 h period and was reduced to about 20% by 10 muM octreotide demonstrating that the uptake of [ (131)I] 12a in this cell line is predominantly mediated by SSTR2. The intracellularly trapped radioactivity in SK-N-SHsst2 cells was substantially higher for [ (131)I] 12a compared to that for [ (125)I]OIBG-octreotate, an isomeric congener of 12a. Because MIBG has more specific NET-mediated uptake than OIBG, this suggests at least a partial role for NET-mediated uptake of [ (131)I] 12a in this cell line. While further refinement in the structure of the conjugate-probably interposition of a flexible and/or cleavable linker between the MIBG and octreotate moieties-may be necessary to make it a substrate/ligand for both NET and SSTR2, this conjugate is demonstrated to be much superior than I-Gluc-TOCA with respect to the uptake in SSTR2-expressing cells.     

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.