Results of radioiodine therapy in 47 patients with distant metastases of differentiated thyroid carcinoma

In the last ten years, 47 patients with distant metastases of differentiated thyroid carcinoma have been treated with 131I following total thyroidectomy. Post-therapy whole body 131I scans revealed detectable uptake in the metastatic lesions in 23 (62%) of 37 patients with lung metastases, 10 (67%) of 15 patients with bone metastases five (71%) of seven patients with mediastinal metastases, and neither of two patients with brain metastases. The concentration of 131I in the metastases was significantly correlated with serum T3 and T4 concentrations, and inversely correlated with serum TSH concentrations. Most of the patients with a strong positive scan were euthyroid, suggesting that thyroid hormones produced by the tumor compensated for hypothyroidism following total thyroidectomy. There was no significant relationship between serum thyroglobulin concentration during T4 replacement therapy and 131I uptake or the efficacy of therapy. Twenty patients with lung (54%), five with bone (33%), two with mediastinal (29%), and none with brain metastases showed tumor regression after treatment. Significantly increased 131I uptake in lung metastases, better therapeutic results and better prognosis were demonstrated in young patients. In conclusion, age, 131I whole body scanning and serum thyroid hormone concentrations are considered to be useful in predicting the efficacy of 131I treatment for distant metastases, especially in the lung.     

Whole-body iodine-131 metaiodobenzylguanidine imaging for detection of bone metastases in patients with paraganglioma: comparison with bone scintigraphy

Iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) therapy is an effective treatment for patients with malignant paraganglioma for which surgical resection is not indicated. We performed high-dose ¹³¹I-MIBG therapy on two patients with malignant paraganglioma and multiple bone metastases. The bone metastases were diagnosed by magnetic resonance imaging (MRI). Metastatic bone lesions were evaluated by whole-body ¹³¹I-MIBG imaging and bone scintigraphy. Whole-body ¹³¹I-MIBG imaging showed extensive metastatic bone lesions, whereas conventional bone scintigraphy did not. There was a remarkable discrepancy between ¹³¹I-MIBG imaging and bone scintigraphy in the diagnosis of metastatic bone lesions of malignant paraganglioma in our two patients. High-dose ¹³¹I-MIBG imaging may detect early stages of bone metastases, compared with bone scintigraphy, in patients with malignant paraganglioma.     

The early detection of metastatic differentiated thyroid cancer using 131I total body scan and treatment with 131I

With the purpose of achieving early detection and performing 131I therapy for metastatic lesions of differentiated thyroid cancer, we studied the clinical findings in 132 patients who underwent 131I total body scanning (131I TBS) between 1981 and 1990. Metastatic lesions were detected only by 131I TBS in 24 (18%) of the 132 patients. Of the 49 patients treated with 131I for metastases, 27 (55%) underwent total thyroidectomy and then had their metastatic lesions treated by 131I less than one year later. In the remaining 22 patients (45%), the metastatic lesions were treated with 131I from 1 to 31 years (mean: 8.4 years) after the initial thyroidectomy. We determined the optimal timing of 131I TBS following radical thyroidectomy to be 3-4 weeks by sequential measurement of the serum thyroid hormones, TSH, and Tg, and determination of the 123I uptake in residual or metastatic cancer of the neck after thyroidectomy. 131I TBS with simultaneous serum Tg determination were performed in 52 patients with metastases. Scans were positive in 43 of the 52 (83%) and the serum Tg level was greater than 10 ng/ml in 46 of the 52 (88%). Serum Tg was elevated in 9 patients with negative scans, while low Tg levels were found in 6 patients with positive scans. 131I therapy was effective in 49 of the 65 treated patients (75%), including 5 cures. Two patients worsened and 6 died. These 8 patients were all older than 56 years of age. Post-therapeutic 131I TBS demonstrated unsuspected metastatic lesions in 7 patients and had a higher detection rate for metastatic lesions than diagnostic 131I TBS. We conclude that 131I TBS with simultaneous Tg determination should be performed to detect metastatic lesions in all patients following positively total thyroidectomy for differentiated thyroid cancer, and that 131I treatment should be given when positive 131I uptake is detected in metastatic or residual cancer.     

Detection of metastatic medullary thyroid cancer with 131I-MIBG scans in Sipple's syndrome

While 131I-meta-iodobenzyl guanidine (131I-MIBG) scanning has made possible the scintigraphic visualization of pheochromocytoma and neuroblastoma, an accumulation of this agent has recently been reported in medullary thyroid cancer. We present the case of a patient with Sipple's syndrome (multiple endocrine neoplasia type IIa), in whom we were able to identify distant metastases and local invasion of medullary thyroid cancer as well as primary thyroid tumour and right adrenal pheochromocytoma, using 131I-MIBG scans. This case highlights the usefulness of 131I-MIBG in the detection of metastatic medullary thyroid cancer and suggests that this agent may also be of therapeutic use in the treatment of tumours.     

Present status and progress of endocrine nuclear medicine

The author reviewed present status and progress of endocrine nuclear medicine including thyroid, parathyroid, adrenocortical, adrenomedullary and somatostatin receptor imaging and also radionuclide therapy of Basedow's disease, metastatic foci of post-operative thyroid cancer and malignant neural crest tumor. Relatively new imaging agents include 99mTc-MIBI and 99mTc-tetrofosmin for parathyroid imaging and 111In-pentetreotide for somatostatin receptor imaging. It is hoped that therapy of malignant neural crest tumors such as metastatic pheochromocytoma and neuroblastoma with 131I-MIBG and somatostatin receptor imaging will be available in Japan as soon as possible.     

Complementary roles of CT and 131I-MIBG scintigraphy in diagnosing pheochromocytoma

Recently 131I-MIBG (metaiodobenzylguanidine), an adrenergic tissue-localizing radiopharmaceutical, has been used for diagnosis of pheochromocytoma. In a retrospective study of 32 patients with pathologically proved primary, metastatic, or recurrent pheochromocytoma, the roles of 131I-MIBG scintigraphy and computed tomography (CT) in pheochromocytoma detection were compared. The two methods were equally accurate in the identification of primary and recurrent pheochromocytoma. 131I-MIBG scanning was more accurate as the initial examination in patients with extraadrenal tumors. In patients with metastatic disease, scintigraphy was preferable to CT because of its nontomographic nature, which permitted imaging of the entire body. Although a positive MIBG scan is diagnostic of pheochromocytoma, CT of extraadrenal tumors (particularly in the chest) has been very useful in planning appropriate surgical intervention. Furthermore, the roles of 131I-MIBG scintigraphy and CT in the detection of pheochromocytoma are complementary because each method has certain limitations.     

Multiple endocrine neoplasia type 2 with malignant pheochromocytoma — Long term follow-up of a case by131I-meta-iodobenzylguanidine scintigraphy—

The case of a 33-year-old Japanese man, who has Multiple Endocrine Neoplasia Type 2 (MEN IIa) (Sipple's syndrome) with malignant pheochromocytoma, is reported. He had survived for twelve years since the initial diagnosis of malignant pheochromocytoma. Within this period, he had undergone 131I-meta-iodobenzylguanidine scintigraphy twice, in 1983 and 1990. This is the first case in Japan of a longterm surviving patient with malignant pheochromocytoma followed up by 131I-MIBG scintigraphy. Although he had no exacerbation of clinical symptoms or urinary catecholamine levels, second scintigraphy clearly showed an increase in the tumor size, new metastasis of the malignant pheochromocytoma and exacerbation of the medullary thyroid carcinoma. Compared with any other roentgenological device and hormonal data, 131I-MIBG scintigraphy was seen to be a good tool for evaluating the localization and the progression of tumors. 131I-MIBG scintigraphy is a useful procedure not only for initial diagnosis but also for judging progression in a case of advanced malignant pheochromocytoma.     

A new medico-nuclear outlook for the diagnosis and treatment of pheochromocytomas: 131I-meta-iodobenzylguanidine (131I-MIBG). Comments on results obtained

The diagnostic and therapeutic potential of 131I-MIBG, the new imaging agent with structural similarity to norepinephrine, was evaluated in 23 patients with a suspect pheochromocytoma. Seven out of 8 benign pheochromocytomas (2 ectopic) were correctly localized with 131I-MIBG scintigraphy (1 false negative). In 2 catecholamine-secreting malignant pheochromocytomas both the primary tumor and the metastases (1 case) were demonstrated. One uncommon case of dopamine-secreting malignant pheochromocytoma, as expected, was not shown. In the remaining 12 cases, found to be "normal" after completing the work-up, distribution of the radiopharmaceutical was evaluated using a semiquantitative grading system. 131I-MIBG scintigraphy proved to be a non invasive and accurate (95%) diagnostic modality, specific for neuroadrenergic tumors. The treatment with 131I-MIBG was also carried out in 2 malignant pheochromocytomas with encouraging results.     

分化型甲状腺癌的治疗进展

分化型甲状腺癌作为一种常见的低恶性肿瘤,通过“外科手术+131I治疗+甲状腺激素抑制治疗”三部曲的规范化治疗方案取得了良好的治疗效果。但部分治疗效果差的分化型甲状腺癌逐渐转化为低分化或失分化的难治性甲状腺癌,只能通过增敏和（或）再分化治疗来增加甲状腺癌细胞摄取131I的能力,以期提高131I治疗甲状腺癌的效果。对上述治疗手段无效的难治性甲状腺癌,靶向药物治疗技术的出现为其提供了广阔的治疗前景。笔者对使用增敏剂、再分化诱导剂和靶向药物治疗技术来提高分化型甲状腺癌治疗效果的研究进展进行了综述。     

Detection of metastatic medullary thyroid cancer with 131I-MIBG scans in Sipple's syndrome

While ¹³¹I-meta-iodobenzyl guanidine (¹³¹I-MIBG) scanning has made possible the scintigraphic visualization of pheochromocytoma and neuroblastoma, an accumulation of this agent has recently been reported in medullary thyroid cancer. We present the case of a patient with Sipple's syndrome (multiple endocrine neoplasia type IIa), in whom we were able to identify distant metastases and local invasion of medullary thyroid cancer as well as primary thyroid tumour and right adrenal pheochromocytoma, using ¹³¹I-MIBG scans. This case highlights the usefulness of ¹³¹I-MIBG in the detection of metastatic medullary thyroid cancer and suggests that this agent may also be of therapeutic use in the treatment of tumours.     

Diagnosis and therapy of neuroectodermal tumors

Computed tomography (CT) and 123I- or 131I-meta-iodo-benzyl-guanidine (MIBG) scintigraphy were compared for accuracy in tumor detection in 47 patients with neuroectodermal neoplasms. MIBG concentration was found in 12 of 13 pheochromocytomas, 12 of 12 neuroblastomas, 5 of 9 carcinoids, and 1 of 4 glomus tumors. MIBG uptake was not observed in medullary thyroid carcinomas, oat-cell carcinomas, Merkel tumors, 1 gastrinoma, and 2 unclassified neuroectodermal neoplasms. With regard to the different tumor manifestations, the sensitivity in detecting pheochromocytomas, neuroblastomas, and carcinoids was 87%, 77%, and 100% for CT, and 83%, 100% and 71% for MIBG scintigraphy, MIBG scintiscan was superior in the detection of small adrenal pheochromocytomas (less than 1 cm diameter) and in the depiction of small bone metastases and bone marrow infiltration from neuroblastoma. In all, 25 cycles of high-dose MIBG therapy were performed in eight patients with surgically incurable tumors (4 malignant pheochromocytomas, 1 neuroblastoma, 3 carcinoids). The total therapeutic activity applied was 3.55-43.29 GBq 131I-MIBG. Tumor kinetics of MIBG were investigated before and during treatment. One patient with metastatic pheochromocytoma has been in complete remission for a follow-up period of 36 months since completion of treatment, and another patient is in partial remission. Tumor reduction or no change was observed in four patients. Two patients died of non-concentrating recurrence and metastases.     

131I治疗分化型甲状腺癌转移灶中甲状腺球蛋白测定和131I-全身显像的意义

目的探讨分化型甲状腺癌转移灶治疗中131I-全身显像(131I-WBS)和甲状腺球蛋白(Tg)测定的意义。方法39例分化型甲状腺癌患者术后4～6周用131I行首次清除残余甲状腺治疗,3～6个月后重复治疗,治疗中131I-WBS和Tg测定同期完成。结果在首次清除残余甲状腺治疗时显像发现淋巴、肺及骨转移灶有11例,其余转移灶于重复治疗时发现。131I治疗分化型甲状腺癌转移灶,以淋巴转移效果最好,肺转移次之,骨转移最差。有8例患者(20.5%)Tg测定与131I-WBS不符。结论131I治疗分化型甲状腺癌转移灶效果好,患者存活率高;131I-WBS和Tg测定在分化型甲状腺癌随访中应联合应用,互相补充。     

分化型甲状腺癌骨转移诊断及疗效评价的核素显像研究进展

分化型甲状腺癌（DTC）骨转移的诊断及疗效评价的核素显像方法较多,放射性核素显像在恶性肿瘤骨转移中的临床应用比较广泛,在DTC骨转移中主要用于骨转移的诊断、术后随访及疗效评价。放射性核素显像目前主要包括SPECT显像和PET显像,前者包括131I显像、99Tcm-MDP显像等,后者包括124I显像、18F-FDG显像、18F-NaF显像等。笔者将放射性核素显像方法在DTC骨转移中的诊断及治疗进展进行综述。     

Computed tomography and 131I-MIBG scintigraphy in the diagnosis of pheochromocytoma

In order to evaluate the usefulness of computed tomography (CT) and 131I meta-iodobenzylguanidine (131I-MIBG) scintigraphy for the localization of pheochromocytoma, a prospective study was undertaken in 23 patients with possible pheochromocytoma. Seventeen tumors were identified in 13 patients. Two tumors were extra-adrenal. CT was superior for locating tumors in the adrenal glands while 131I-MIBG scintigraphy was more useful in the detection of extra-adrenal pheochromocytoma. Together with adrenal and extra-adrenal pheochromocytoma, the sensitivity for locating the tumor was calculated as 82 per cent (14/17) for CT and 76 per cent (13/17) for 131I-MIBG scintigraphy, respectively. One adrenal tumor (1 cm in size) only was missed by both methods. No false positive CT scans of 131I-MIBG scintigraphy were obtained in the remaining 10 patients who had possible pheochromocytoma but were excluded. These results indicated that CT and 131I-MIBG scintigraphy were both useful tools for detecting pheochromocytoma.     

Iodine-131 MIBG scintigraphy of the extremities in metastatic pheochromocytoma and neuroblastoma

Iodine-131 MIBG scintigraphy may be used to determine the presence or absence of metastases to the appendicular skeleton in malignant pheochromocytoma and neuroblastoma. Normal bones show no uptake of [131I]MIBG and the joints are seen as photon-deficient areas surrounded by background muscle activity. Discrete concentrations of radioactivity in bone are often seen in patients with malignant pheochromocytoma and neuroblastoma. Bone marrow involvement in neuroblastoma may be indicated by diffuse uptake of [131I]MIBG or focal accumulation at the metaphyses. Uncommonly, bone involvement may not be displayed by the [131I]MIBG images. Since conventional bone scanning agents may also fail to detect these tumors, skeletal scintigraphy with both [131I]MIBG and [99mTc]MDP is necessary to reliably stage malignant pheochromocytoma and neuroblastoma.     

The assessment of clinical usefulness of 131I-MIBG scintigraphy for localization of tumors of sympathetic and adrenomedullary origin--a report of multicenter phase III clinical trials]

A phase III clinical study of 131I-metaiodobenzylguanidine (131I-MIBG) was performed in 66 patients with tumors of sympathetic and adrenomedullary origin, including 32 patients with suspected pheochromocytoma, 25 with suspected neuroblastoma, 7 pre- or postoperative medullary carcinoma of the thyroid and each with carcinoid and suspected Sipple's syndrome. A total of 150 sites which were confirmed for presence (72 sites) or absence (78 sites) of tumors were examined on 131I-MIBG scintigrams. True positive ratio of the scintigraphy was 84.7% (61/72) and true negative ratio was 94.9% (74/78). Positive scintigraphy was obtained in 86.5% (32/37) of pheochromocytoma, 78.6% (22/28) of neuroblastoma and 100% (6/6) of medullary carcinoma of the thyroid. Accumulation of 131I-MIBG was seen in 16.8% of normal adrenal glands. Neither adverse reactions nor abnormal laboratory findings were noted in relation to 131I-MIBG injections. Our study indicates that 131I-MIBG is a safe and clinically useful radiotracers for the visualization and localization of tumors of sympathetic and adrenomedullary origin.     

Seven cases of brain metastasis from papillary thyroid carcinoma

Brain metastases from differentiated thyroid carcinoma are extremely rare and carry a poor prognosis. We describe here clinical details of 7 cases of brain metastases from papillary thyroid carcinoma. Of 153 patients with metastases from differentiated thyroid carcinoma (papillary in 123, follicular in 30) treated at our institution between 1981 and 1999, 7 patients (4.6%) had brain metastases. Histologically, the primary tumor was papillary carcinoma in all 7 cases. Four were males and 3 were females. The median age at first diagnosis of distant metastases was 63 yr (range, 47-76 yr). Of these patients, one had brain metastases only and six had metastases to the lungs as well. Five of these patients were treated with 131I. Three of these 5 patients had marked uptake in the metastases (131I positive) on post-therapy 131I scans and another 2 patients had no significant activity (131I negative) in both pulmonary and brain metastatic lesions. One of 3 patients with 131I positive lesions had intense activity in the brain tumor, but no uptake in multiple pulmonary metastatic tumors. In a patient with 131I positive brain metastases, the tumors progressed rapidly after 131I therapy. In another one patient, acute hemorrhage of the tumor occurred four days after 131I therapy, requiring surgical removal. Loner case of 131I negative 2 patients was treated with radiosurgery (gamma-knife) and complete reduction in tumor volume was observed. On the other hand, one of 2 patients receiving no 131I therapy had radiosurgery (x-knife) and remaining one received conventional external radiation and chemotherapy for small solitary brain and pulmonary metastatic tumors. These therapeutic interventions were useful in both cases. The mean length of survival after the development of brain metastases in the five patients who died of the disease was 30 months. One patient treated with x-knife has been alive at 21 months and another one who has 131I uptake in the brain tumor without uptake in lung lesions has been alive 15 months after diagnosis of brain metastasis. These results indicate that it is important to detect brain metastasis by imaging techniques and Tg measurements and give treatment as early as possible since the brain is the third most common distant metastatic site and the prognosis is poor.     

手术联合~(131)I治疗分化型甲状腺癌疗效探讨

目的探讨手术联合131I对分化型甲状腺癌的治疗效果。方法将160例分化型甲状腺癌(DTC)患者根据术后是否接受131I治疗分为观察组与对照组各80例。观察组给予手术+放射性131I治疗,对照组给予手术+优甲乐治疗,观察两组治疗情况。结果观察组首次"清甲"成功率为71.3%,甲状腺全切者首次"清甲"成功率显著高于次全切者(P<0.01)。术后131I治疗对颈部淋巴结转移患者总有效率为95.3%,肺转移患者为82.6%,骨转移患者为64.3%。服用131I后1周内不良反应发生率为38.8%(31/80),其中甲状腺全切者不良反应发生率显著低于次全切者(P<0.05)。随访至今,观察组复发转移发生率与患者存活率均显著优于对照组(P<0.05)。结论手术+131I治疗DTC可在术后有效清除残留甲状腺组织及残留的微小癌,同时可对颈部淋巴结转移及肺转移灶进行治疗,可降低复发及转移率,远期效果较好。     

Radioiodinated MIBG in paraganglioma and pheochromocytoma: previous results and early experiences using no-carrier-added MIBG

The majority of pheochromocytomas and paragangliomas are benign, with malignancy occurring in approximately 10% of pheochromocytoma patients. The malignancy rate among paragangliomas is 15–35% or higher if associated with succinate dehydrogenase B gene mutations. The 5-year mortality rate in malignant pheochromocytoma and paraganglioma is nearly 50%. Malignancy of both pheochromocytoma and paraganglioma is determined by the existence of metastasis or local invasion and not by the cellular characteristics. There are no known clinical, biochemical or histopathological differences between pheochromocytoma and paraganglioma.Metaiodobenzylguanidine (MIBG) radiolabeled with either ¹²³I or ¹³¹I has been used to diagnose neuroendocrine tumors such as paraganglioma and pheochromocytoma, and ¹³¹I-MIBG has been used to treat these tumors. The role of radioiodinated MIBG in treating neuroendocrine tumors is still being evaluated. More recently, no-carrier-added (nca) MIBG has become available, and the advantages of nca MIBG over ca MIBG are being demonstrated. This article reviews the biology of paragangliomas and pheochromocytomas, the role of MIBG imaging in the diagnosis of these tumors and the role of both ca and nca ¹³¹I-MIBG in the treatment of these tumors. New data on nca ¹³¹I-MIBG in the therapy of these tumors are included.     

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma.

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4-16 years by means of regular Tg measurements, (131)I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9+/-310.6 vs 15.9+/-19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of (131)I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, (131)I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up.