Biodistribution studies of bee venom and spider toxin using radiotracers

The use of radiotracers allows the understanding of the bioavailability process, biodistribution, and kinetics of any molecule labelled with an isotope, which does not alter the molecule's biological properties. In this work, technetium-99m and iodine-125 were chosen as radiotracers for biodistribution studies in mice using bee (Apis mellifera) venom and a toxin (PnTX2-6) from the Brazilian "armed" spider (Phoneutria nigriventer) venom. Incorporated radioactivity was measured in the blood, brain, heart, lung, liver, kidney, adrenal gland, spleen, stomach, testicle, intestine, muscle, and thyroid gland. Results provided the blood kinetic parameter, and different organs distribution rates.(AU)

Blockade of neuronal nitric oxide synthase abolishes the toxic effects of Tx2-5, a lethal Phoneutria nigriventer spider toxin.

The primary goal of this study was to determine whether Tx2-5, a sodium channel selective toxin obtained from the venom of the spider Phoneutria nigriventer, produced penile erection by means of nitric oxide mechanism. Toxin identity was analyzed by MALDI-TOF, ES-MS and N-terminal amino acid sequencing. Pretreating mice with the non-selective nitric oxide synthase (NOS) inhibitor N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and the selective neuronal-NOS inhibitor 7-Nitroindazole (7-NI) prior to Tx2-5 i.p. (10 microg/25 g mouse) injection challenged the hypothesis above. Controls were injected with the D-isomer or DMSO or saline. Results demonstrated that L-NAME inhibited penile erections in about half the animals treated, while 7-NI completely abolished this effect. Interestingly 7-NI also abolished all the other symptoms of intoxication induced by Tx2-5, including salivation, respiratory distress and death. Tx2-5 killed all the animals of the control group and no one in the 7-NI-treated group. We conclude that (1) intraperitoneal injections of Tx2-5 induce a toxic syndrome that include penile erection, hypersalivation and death by respiratory distress or pulmonary edema; (2) pretreatment with the non-selective NOS inhibitor L-NAME reduces the penile erection and partially protects from the lethal effects of Tx2-5; (3) pretreatment with the nNOS-selective inhibitor 7-NI completely abolishes all the toxic effects of Tx2-5, including penile erection and death suggesting that nNOS is the major player in this intoxication; (4) toxins from other animals that affect sodium channels in the same way as Tx2-5 and induce similar toxic syndromes may have as a major common target, the activation of nitric oxide synthases.

Solitary liver metastasis from Hürthle cell thyroid cancer: a case report and review of the literature.

Metastasis to the liver from thyroid cancer is a rare event with a reported frequency of 0.5%. Metastatic liver involvement from differentiated thyroid cancer (DTC) is nearly always multiple or diffuse and usually found along with other distant metastases (lung, bone and brain). The authors describe a patient with a solitary liver metastasis from Hürthle cell thyroid cancer, which appeared during long-term follow-up. The lesion was diagnosed by progressive increase of thyroglobulin in the serum and imaged with I-131 whole body scan, ultrasonography, magnetic resonance imaging (MRI) and F-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) scan. For patients with a Tg level above some arbitrary limit, the administration of a large dose (3.7-5.5 GBq; 100-150 mCi) of I-131, in order to obtain a highly sensitive Tx whole body scan (WBS), remains the best diagnostic strategy. However, on very rare occasions, physiological enteric radioactivity can hide possible abdominal lesions and further indepth studies, such as FDG-PET scans, are sometimes necessary.

[New perspectives in diagnosis and therapy of endocrine gastroenteropancreatic (GEP) tumors with somatostatin analogues]. / Nuove prospettive nella diagnosi e terapia dei tumori endocrini gastroenteropancreatici (GEP) con analoghi della somatostatina.

In the last decade important progresses have been obtained in the diagnosis and therapy of endocrine gastroenteropancreatic (GEP) tumors, mainly derived from the somatostatin receptors characterization and the introduction of long acting somatostatin analogues. Receptorial scintigraphy with radio-labeled analogues (Octreoscan) is the first choice investigation for staging and follow-up of endocrine GEP tumors, thanks to the high sensitivity in revealing the primary tumor and metastases, and for its capability to reveal lesions that are not identified by other imaging methods. Moreover, somatostatin analogues uptake by tumors allow us to use radiopharmaceutical compounds for advanced disease treatment. Between the radio-labeled drugs until now studied, interesting results have been obtained by DOTA-lanreotide (MAURITIUS), DOTA0 Tyr3-octreotide (DOTATOC) and DOTA0 Tyr3-octreotate, bound to beta-emitting radio-isotope suitable for therapeutic use. In the field of the pharmacological therapy of GEP tumors, the clinical trials show that somatostatin analogues reduce the symptoms related to functionally active tumors and stabilize or slow tumor growth improving the patient quality of life. Although somatostatin analogues alone could not be able to cure GEP tumors, their early utilization in association with surgical debulking of primary tumor and metastases, embolization or chemoembolization, and interferon, chemotherapy and radio-metabolic therapy (mainly directed to the destruction of micrometastases), increases the possibility of a radical therapeutic intervention. The continuous evolution of pharmacological research provides always new analogues (octreotide LAR, lanreotide, vapreotide, BIM-23244, BN 81644, PTR-3173, BIM-23A387, SOM-230, etc.) with different pharmacokinetic and receptorial properties and acting with more effectiveness in the different individual clinical situations. In this context there have been recently introduced also the "chimeric" analogues. On the other hand, the widespread utilization of molecular biology and immunohistochemical methods can allow, in perspective, to better define the receptorial pattern of individual endocrine tumors, after their surgical removal. The necessity to integrate endocrinological, nuclear medicine, surgical, oncologic and laboratory competencies behaves a multidisciplinary approach based on the utilization of diagnostic-therapeutic protocols supplying comparable results. It does not appear unjustified to expect, in the future, a scenery of more "individual" and more effective therapies for patients affected by GEP tumours.

Treatment of advanced neuroblastoma: feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and multiple drug chemotherapy.

Biological and clinical observations suggest that initial marked reduction of resistant clones may be critical in any attempt to improve long-term results in advanced neuroblastoma (NB). The aim of this pilot study is to determine short-term toxicity and efficacy of a new therapeutic model based on the simultaneous use of multiple drug chemotherapy and specific irradiation using 131-I-MIBG. The study population consisted of 21 patients, from 1 to 8 years of age with good 131-I-MIBG uptake. 16 extensively pre-treated patients with refractory or relapsed disease were divided into 2 groups. In Group 1 (9 patients) the basic chemotherapy regimen consisted in cisplatin at the dose of 20 mg/m(2) i.v. per day infused over 2 h, for 4 consecutive days; on day 4 Cy 2 g/m(2) i.v. was administered over 2 h followed by Mesna. Group 2 (7 patients) was treated with basic chemotherapeutic regimen plus VP16 and Vincristine. VP16 at the dose of 50 mg/m(2) i.v. per day was administered as a 24 h infusion on days 1-3; Vincristine 1.5 mg/m(2) i.v. was administered on days 1 and 6. On day 10 a single dose of 131-I-MIBG (200 mCi) with a high specific activity (>1.1 GBq/mg) was administered to both Groups by i.v. infusion over 4-6 hours. A further 5 patients were treated at diagnosis: 2 with the same regimen as Group 1 and 3 with the same as Group 2. The severity of toxicity was graded according to World Health Organization (WHO) criteria. Assessment of tumour response was monitored 4-6 weeks after the beginning of combined therapy (CO-TH). Response was defined according to INSS (International Neuroblastoma Staging System) criteria. No extra-medullary toxicity was observed in any patient. Haematological toxicity was the only toxicity observed and seemed mainly related to chemotherapy. Myelosuppression was mild in the 5 patients treated at diagnosis. No serious infections or significant bleeding problems were observed. In the 16 resistant patients, 12 PR, 1 mixed response and 3 SD were obtained. In the 5 patients treated at diagnosis 2 PR, 1 CR and 2 VGPR were observed. No alteration in 131-I-MIBG uptake was observed after the chemotherapy preceding radio-metabolic treatment. The therapeutic results of this pilot regimen of CO-TH resulted in a high percentage of major response after only a single course in both resistant patients and patients treated at diagnosis. Because of the minimal toxicity observed in patients studied at diagnosis so far, there is room for gradual intensification of the treatment. It is to be hoped that this suggested novel approach may represent an important route of investigation to improve final outcome in patients with advanced NB.

Gyroxin fails to modify in vitro release of labelled dopamine and acetylcholine from rat and mouse striatal tissue.

Gyroxin fails to modify in vitro release of labelled dopamine and acetylcholine from rat and mouse striatal tissue. Gyroxin is a thrombin-like peptide with amidasic, esterasic and fibrinogenolitic activities, found in the venom of snakes like Lachesis muta muta and Crotalus durissus terrificus. Intravenous injections of small doses of gyroxin induce a typical barrel rotation behaviour that has been thought to be a neurotoxic effect. The aim of this study was to determine whether gyroxin-induced barrel rotation behaviour involves changes in neurotransmitter release. Gyroxin was isolated from crude venoms by gel filtration and affinity chromatography. Its properties were determined by assaying esterasic, amidasic and fibrinogenolitic enzymatic activities and tested for barrel rotation behaviour. Neurotransmitter release tests employed rat and mouse superfused brain striatal chopped tissue preloaded with [(3)H]-dopamine, [(3)H]-acetylcholine or in a double labelling procedure. They were stimulated by 20mM K(+) in control conditions or in the presence of several concentrations of toxins. Crotoxin and crotamine were used as positive controls. Gyroxins failed at modifying both basal and stimulated neurotransmitter releases, suggesting a lack of direct neurotoxic effect. We therefore suggest that gyroxin may not be a neurotoxin but rather, induces this behavioural syndrome by other means possibly related to haemodynamic disturbance. The possible role of vasopressin is discussed.

Relationship between myocardial 123I-metaiodobenzylguanidine scintigraphic uptake and heart rate variability in patients with syndrome X.

BACKGROUND: We have recently demonstrated a striking impairment in cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) in most patients with syndrome X. In this study we investigated the relationship between cardiac MIBG defects and cardiac autonomic activity in these patients. METHODS: MIBG myocardial scintigraphy and time-domain and frequency-domain heart rate variability (HRV) were compared in 11 syndrome X patients and 10 healthy controls. Cardiac MIBG uptake was assessed by the heart/mediastinum ratio and a cardiac MIBG uptake defect score (higher values = lower uptake). RESULTS: The heart/mediastinum ratio was lower (1.71 +/- 0.6 vs 2.19 +/- 0.3, p = 0.03) and MIBG uptake score higher (37.1 +/- 32 vs 4.0 +/- 2.5, p = 0.005) in syndrome X patients, whereas average HRV values did not differ between the two groups. However, while there were no correlations between MIBG uptake and HRV in controls, in syndrome X patients both the heart/mediastinum ratio and MIBG uptake score correlated significantly with two HRV parameters, specific for vagal activity: the square root of the mean squared differences of consecutive RR intervals (r = 0.73, p = 0.01, and r = -0.67, p = 0.02, respectively), and high frequency (r = 0.64, p = 0.03, and r = -0.74, p = 0.009, respectively). CONCLUSIONS; In patients with syndrome X, the impairment in cardiac MIBG uptake was associated with a reduction in HRV indexes mainly reflecting vagal modulation of sinus node, thus suggesting that a predominance of cardiac adrenergic activity may be present in those with abnormal cardiac MIBG scintigraphy.

Role of nuclear medicine in the diagnosis and therapy of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) originates in the parafollicular cells (C cells) of the thyroid, secreting both calcitonin and CEA. Genetic and biochemical testing allow early pre-clinical identification of familial forms. Sporadic MTC usually presents as a solitary palpable thyroid nodule and in most cases the definitive diagnosis is established only at the time of surgery. Nuclear medicine procedures, which play a minor role in the preoperative evaluation of MTC, are essential in postoperative follow-up to detect residual and/or recurrent tumor. A number of radiopharmaceuticals are able to visualize MTC lesions with considerable advantages in diagnosis and prognosis, some of them having also a therapeutic role. Among them, 99mTc[V]DMSA shows the highest diagnostic sensitivity and is considered by many authors the radiopharmaceutical of choice in the postoperative work-up of MTC. Radioiodinated MIBG, in spite of its high specificity has a poor sensitivity (30%); however it is useful for the identification of pheochromocytoma and, in patients showing MIBG uptake in tumoral lesions, high activities of 131I-MIBG may be used for therapy. 111In labeled octreotide detects lesions which express somatostatin receptors; a positive scintigraphic result seems to give also prognostic information (higher uptake in slow-growing lesions) and provides the basis for treatment with octreotide or lanreotide and 111In or 90Y-labeled octreotide analogues. Interesting perspectives are offered by 18F-FDG PET and monoclonal anti-CEA labeled antibodies; the latter may be also used for therapy.

Diagnostic imaging of euthyroid goiter.

In diffuse or nodular euthyroid goiter, diagnostic imaging is indicated to define, by sonography, the morphology, size and structure of the goiter and to evaluate, by scintigraphy, the regional thyroid function. The instrumental diagnosis of thyroid nodule is essentially based on sonography, scintigraphy and (US-guided) needle aspiration cytology. The evaluation of some sonographic findings (echogenicity, calcification, lesion margins and presence of peripheral ring) may direct to the differentiation of a benign or malignant lesion. The role of color Doppler in the characterization of thyroid nodules is still controversial. Scintigraphy provides information on nodular function, being also the only exam able to show the presence of autonomously functioning thyroid tissue ("hot" nodule), whose diagnosis allows to rule out the presence of thyroid carcinoma with a very strong probability. In intrathoracic goiter, CT and MRI and indicated to show the continuity with the cervical thyroid and to define the relationships with adjacent structures. Radioiodine scintigraphy shows with high (> 90%) diagnostic accuracy the thyroid nature of a mediastinal mass (plunging goiter).

Nuclear medicine therapy of pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas are rare catecholamine-producing tumors which arise from chromaffin tissue. When a pheochromocytoma/paraganglioma is suspected, biochemical confirmation is based on 24-hour urinary excretion rates of catecholamines and their metabolites (metanephrines, VMA, etc.). Following biochemical confirmation non invasive imaging techniques such as CT and/or MR of the abdomen and 123I-MIBG scintigraphy are performed to localize the tumor. 111In-octreotide may also be applied, mainly to localize head and neck chemodectomas. Malignant paragangliomas of either adrenal or extra-adrenal origin show a variable natural history: from a locally invasive indolent tumor to a highly aggressive malignancy. Surgery with complete resection or debulking of the primary tumor is the standard treatment. External radiotherapy and chemotherapy are usually scarcely effective. An alternative treatment is 131I-MIBG therapy which is performed with high specific activity 131I-MIBG. Usually a standardized dose ranging from 3.7 to 9.1 GBq of 131I-MIBG is administered by slow i.v. infusion. In advanced stage cases 131I-MIBG therapy aims at symptom palliation and tumor function reduction as well as at tumor arrest or tumor regression. In these cases MIBG therapy allows prolonged survival and good quality of life. In less advanced cases the purpose of MIBG therapy is to complement surgery and to achieve the total eradication of the tumor. Non functioning malignant paraganglioma can some time also concentrate MIBG and can be treated with high doses of the tracer. 131I-MIBG therapy is a safe treatment and is usually well tolerated by the patient (with rather low myelotoxicity).

Severe thyrotoxicosis due to functioning pulmonary metastases of well-differentiated thyroid cancer.

We report two cases of thyrotoxicosis resulting from hyperfunctioning lung metastases from differentiated thyroid cancer. In both patients, a simultaneous diagnosis of thyrotoxicosis and metastatic thyroid cancer was made, based on thyroid function tests as well as 131I whole-body scans showing low thyroid uptake of radioiodine and multiple foci of intense 131I uptake in the lungs. After total thyroidectomy (performed in Patient 2 only) and 131I therapy (cumulative dose of 12.3 GBq in Patient 1 and 9.6 GBq in Patient 2), there was a rapid clinical improvement with significant reduction of the pulmonary metastatic disease in both patients: Patient 1 became euthyroid, while Patient 2 became hypothyroid. Analysis of the 54 cases reported in the literature, including the 2 cases described here, shows this to be a very rare cause of thyrotoxicosis and one that can pose serious problems for both the diagnostic evaluation and choice of therapeutic strategy when compared with the much more common nonhyperfunctioning metastases from thyroid cancer. Lesser degrees of thyroid hormone secretion by differentiated thyroid cancer may be detected and exploited diagnostically by the chromatographic analysis of serum for endogenously labeled thyroid hormones after 131I administration.

Specificity of radioiodinated MIBG for neural crest tumors in childhood.

UNLABELLED: The high sensitivity of metaiodobenzylguanidine (MIBG) scintigraphy for sympathomedullary tumors such as neuroblastoma and pheochromocytoma is well documented. The specificity of MIBG scintigraphy for these tumors is also high but has been incompletely characterized for other neural crest tumors and non-neural crest tumors of childhood. METHODS: The medical records and MIBG scans of all children who had undergone MIBG scintigraphy for known or suspected neuroblastoma or pheochromocytoma were retrospectively reviewed at five major referral centers. Those patients found to have pathologies other than neuroblastoma or pheochromocytoma form the basis of this study. RESULTS: One hundred children with a total of 110 lesions met the inclusion criteria. All had negative MIBG scans except 1 of 2 children with infantile myofibromatosis, 1 of 2 with neuroendocrine carcinomas, 1 of 2 with pancreaticoblastomas and 1 of 10 with primitive neuroectodermal tumors. CONCLUSION: MIBG scintigraphy is highly specific for neuroblastoma and pheochromocytoma. Only 4% (4/100) of nonsympathomedullary tumors (non-pheochromocytoma and non-neuroblastoma) in childhood showed MIBG uptake, of which only 2% (2/100) were of non-neural crest origin.

Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy.

BACKGROUND: Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries). METHODS AND RESULTS: To evaluate cardiac adrenergic nerve function, we performed [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by 201Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3, P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study. CONCLUSIONS: In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.

Unusual false-positive radioiodine whole-body scans in patients with differentiated thyroid carcinoma.

Radioiodine whole-body imaging is the most accurate method in the diagnosis of metastases from differentiated thyroid cancer. However, false-positive images rarely occur. The authors report unusual cases of thymic hyperplasia and post-traumatic skull changes mimicking mediastinal, skull, or cerebral metastases. Nonthyroidal causes were diagnosed by other radionuclide studies (bone and brain scintigraphy) and CT scans. Follow-up and undetectable thyroglobulin levels helped confirm the benign cause.

131I-MIBG therapy of neural crest tumours (review).

Due to its diagnostic application, consideration was given to the therapeutic potential of 131I-MIBG in neural crest tumours, mainly in malignant pheochromocytomas, paragangliomas, neuroblastomas (NB), carcinoids and medullary thyroid carcinomas (MTC). The therapeutic procedure consists of a) thyroid blockade; b) administration of high specific activity 131I-MIBG; c) single doses, varying from 3.7 to 9.5 GBq, given by slow i.v. infusion (2-3 hours); d) monitoring of the patient during the infusion of the tracer. Targeted radiotherapy with 131I-MIBG in malignant pheochromocytomas, paragangliomas, carcinoids and medullary thyroid carcinomas, was shown to be effective with partial reduction of tumoral lesions (mainly in pheochromocytomas with 58% of objective responses) and palliation in metastatic tumors; in a few pheochromocytomas also succeed in eradicating the residual/recurrent tumor. In patients with stage IV NB who failed to respond to or relapsed after conventional chemotherapy, MIBG therapy showed an important palliative role. A significant therapeutic improvement in the outcome of stage III and IV NB patients was obtained by introducing 131I-MIBG as a first line therapy, partial or even complete responses occurring in more than 60% of the cases treated. Experiences combining chemotherapeutic agents and 131I-MIBG are also in progress with encouraging results. MIBG therapy is well tolerated; toxicity is limited to minor hematologic toxicity and patients generally recover spontaneously. The risk of pancytopenia rises in patients with bone and/or bone marrow metastases; in these cases bone marrow harvesting is recommended. An alternative approach to 131I-MIBG therapy in MTC uses radiolabeled monoclonal antibodies. A novel immunotargeting method, which includes a bispecific antibody and 131I as a radiolabel, seems to be very promising.

Potential use of iodine-123 metaiodobenzylguanidine radioaerosol as a marker of pulmonary neuroadrenergic function.

Iodine-123 metaiodobenzylguanidine (123I-MIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of 123I-MIBG? (2) Is the pulmonary distribution of inhaled 123I-MIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled 123I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized 123I-MIBG; (2) a quantitative evaluation of the lung distribution of 123I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) and (3) an assessment of 123I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with 99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an "MIBG group" and a "DTPA group" (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized 123I-MIBG ranged between 97.18% and 98.70%. The lung distribution of 123I-MIBG, as judged by the aerosol penetration index, was identical to that of 99mTc-DTPA under all study conditions. The 123I-MIBG clearance rate was slower than that of 99mTc-DTPA under baseline conditions (135+/-32 min vs 69+/-27 min, P<0.01) and increased significantly after propranolol administrations, while the 99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of 123I-MIBG; (2) the lung distribution of 123I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of 123I-MIBG reflects the functional status of the neuroadrenergic system of the lungs. Thus this scintigraphic method is suitable for research and perhaps for future clinical use.

Optimal use of the 131-I-metaiodobenzylguanidine and cisplatin combination in advanced neuroblastoma.

Neuroblastoma (NB), a childhood radiosensitive tumor, is very aggressive and malignant, in its disseminated form, despite very intensive chemotherapy, prognosis continues to be dismal. Owing to its capacity to concentrate in NB lesions, large doses of 131-I-MIBG, have given very encouraging therapeutic results in patients resistant to conventional therapy as well as at diagnosis. We recently reported the first attempt in combination therapy (CO-TH) using 131-I-MIBG and cisplatin. This new form of CO-TH appears very effective in obtaining a rapid and excellent response in relapsed patients. In this report, we describe the results of further experience with CO-TH in disseminated NB. We have attempted to verify to what extent interaction between the effects of the two agents may produce therapeutic benefit, and we have sought the optimization of CO-TH use. Three stage IV NB patients were treated with CO-TH. The following treatment schedule, was planned: day 1, cisplatin 50 mg/m3 i.v. over 6 h; day 2, 131-I-MIBG 100-130 mCi at high specific activity (-1.1 Gbq/mg) i.v. over 6 h followed, a week later, by the same treatment combination. The therapeutic results were encouraging. However, hematological toxicity continued to represent a major limiting factor. In view of the overall effectiveness of CO-TH, at the price of lasting hematological toxicity, it may be indicated as a consolidation regimen some time before conditioning chemotherapy for autologous bone marrow transplantation.

Disseminated bone marrow metastases of insular thyroid carcinoma detected by radioiodine whole-body scintigraphy.

We present 131I scintigraphic findings in a patient with insular carcinoma of the thyroid showing diffuse abnormal uptake throughout the skeleton. The scintigraphy closely resembled the pattern of [131I]MIBG distribution in children with bone marrow metastases of neuroblastoma. The extent of involvement was underestimated by bone scintigraphy and radiography. Insular carcinoma of the thyroid in the bone marrow was subsequently demonstrated by biopsy. The patient was treated with 242 mCi 131I given in two courses, which led to severe myelosuppression and died as a result of progressive disease and severe pancytopenia 10 mo after initial therapy.

Radiolabeled somatostatin analog scintigraphy in medullary thyroid carcinoma and carcinoid tumor.

The aim of this study was to evaluate the effectiveness of a recently developed radiolabelled somatostatin analog (111In-pentetreotide) for the detection and localization of both medullary thyroid carcinoma (MTC) and carcinoid tumors, and to compare the results obtained with the results of 99mTc(V)-DMSA, and radioiodinated MIBG imaging. 111In-pentetreotide scintigraphy was performed in 9 patients with MTC and in 9 patients with carcinoid tumor. Whole body and SPECT studies were performed at 4 and 24 hours post-injection. SMS scintigraphy gave a positive result in 5 out of 7 patients with proven MTC lesions, and in 7 out of 9 patients with known lesions of carcinoid tumor. It gave a negative result in 2 MTC patients with high levels of calcitonin but with no evidence of disease at conventional diagnostic modalities. The scintigraphic results were comparable with those obtained with 99mTc(V)-DMSA in MTC and were superior to those of radioiodinated MIBG in both MTC and carcinoid tumors. When compared with the modifications of calcitonin levels brought about by the acute administration of octreotide ("Octeotride test"), these correlated well in 8 out of 9 patients studied.