Autoradiographic analysis of [14C]deoxy-D-glucose in thyroid cancer xenografts: A comparative study with pathologic correlation

An experimental model of thyroid cancer was prepared for evaluating the accumulation of [¹⁴C]deoxy-D-glucose ([¹⁴C]DG) in thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSHin vitro. The histological sections of the xenografts resected from the¹³¹I treated nude mice mainly consisted of structures showing follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the thyroid follicular epithelium. By comparing autoradiographic accumulation patterns of [¹⁴C]DG and histopathological examinations, it was found that the uptake of [¹⁴C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues. It is suggested that the degree of [¹⁴C]DG content reflects not only tumor cell viability and proliferation but also the inflammatory and degenerative reaction accompanying tumor cell growth.     

131I和132I致大鼠甲状腺滤泡上皮细胞核的形态计量学改变

目的 为放射性碘危害与医学防护的研究提供资料。方法 应用图像分析技术和形态计量学方法，测量了＾１３１、＾１３２Ｉ注往后２０个月大鼠甲状腺滤泡上皮细胞核的形态计量学参数的变化。结果 各剂量组滤泡上皮细胞核截面积、等效直径增大，形态因子明显小于对照组（Ｐ〈０．０５或Ｐ〈０．０１），异形指数明显大于对照组（Ｐ〈０．０５￣Ｐ〈０．０１），体积密度，表面积密度、数密度呈先增加后减少的变化特点。结论表明细胞受     

Electroporation: a novel approach to enhance the radioiodine uptake in a human thyroid cancer cell line.

Radioiodine has been the best choice of treatment for differentiated thyroid cancer. Loss of the ability to concentrate iodide makes thyroid cancer cells refractory to radioiodine therapy. Therefore, the methods that enhance the uptake of radioiodine may have significant therapeutic effect. Electroporation involves the application of short high-voltage electric pulses which transiently permeabilize the plasma membrane, allowing entry of the otherwise impermeable molecules. The aim of our study was to use electroporation for incorporating radioiodine into a non-iodine concentrating thyroid cell line. Cultured WRO thyroid cancer cells that do not incorporate iodine due to the lack of the specific transporter protein incorporated significant amounts of radioiodine after electroporation. The uptake of radioiodine by electroporation showed dependence on the electric field, external concentration of the iodine, time and the temperature of incubation. The incorporated radioiodine was retained over a period of 24 h. The retainability of the incorporated iodine may have a significant effect on the tumoricidal properties if validated in vivo.     

The interpretation of 131I scans in the evaluation of thyroid cancer,with an emphasis on false positive findings

Radioiodine has aided the management of differentiated thyroid cancer for several decades. Most thyroid cancers retain the ability to trap iodine, and radionuclides of iodine can be used both diagnostically and therapeutically. The availability of sensitive diagnostic tests, coupled with the ability to deliver targeted therapy, gives physicians the ability to manage thyroid cancer better than with any other type of cancer. The correct interpretation of radioiodine scans is critical in the appropriate management of patients with thyroid cancer. False positive findings do occur. A radioiodine scan showing abnormal uptake outside the thyroid bed must be studied carefully and alternative reasons for the finding must be considered. The scan should be analysed systematically. Is there residual thyroid? If so, what is the 48 or 72 h neck uptake? Radioiodine uptake in the salivary glands, stomach, gastrointestinal and urinary tracts should be acknowledged as physiological. Diffuse uptake is seen in the liver in most patients with functioning thyroid at the time of their post-therapy scan. When there is uptake of the radioiodine outside these regions, contamination must be considered. A variety of cases illustrating true positive, true negative, and false positive findings is presented in this review, and the causes and consequences of misinterpretation of radioiodine scans are discussed.     

FDG-PET performed concurrently with initial I-131 ablation for differentiated thyroid cancer

Objective  

Differentiated thyroid cancers (DTCs) are commonly treated by total thyroidectomy followed by I-131 radioiodine ablation to eradicate any residual thyroid tissue and to detect any metastatic lesions on post-treatment whole body scans (TxWBS). However, some DTCs do not trap iodine, resulting in negative whole body scanning. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) has proven to be a valuable diagnostic technique for detecting many types of malignant tumors and metastases. The purpose of this study was to evaluate FDG-PET performed concurrently with initial I-131 ablation for its ability to detect lymph node metastasis and for its role in the management of DTC patients.     

Radioimmunoscintigraphy of human pancreatic carcinoma xenografts in nude mice with131I-labeled monoclonal antibody

Encouraged by reports of radioimmunoimaging of colorectal carcinomas and by examining an immunohistochemical report on resected pancreas cancer tissues, we studied the diagnostic potential of radioimmunoimaging with the radioiodinelabeled monoclonal antibody to the surface antigen of a pancreas cancer cell line. A monoclonal antibody (MoAb; HC-1) to a human pancreas cancer cell line (HGC25)5 was labeled with radioiodine and injected into athymic nude mice implanted with human pancreas cancer cells. Antibody HC-1 was cleared from the circulation and accumulated significantly in the implanted tumor sites.     

Technetium-99m tetrofosmin single photon emission computed tomography to detect metastatic papillary thyroid carcinoma in patients with elevated human serum thyroglobulin levels but negative I-131 whole body scan

AIM: The aim of this study was to evaluate the effectiveness of technetium-99m tetrofosmin (Tc-99m TF) single photon emission computed tomography (SPECT) of the neck and chest to detect metastatic lesions in papillary thyroid carcinoma (PTC) after near total thyroidectomy and radioiodine (I-131) treatment in patients who present with elevated serum human thyroglobulin (hTg) levels but negative I-131 whole body scan (WBS). MATERIALS AND METHODS: Twenty patients with PTC treated by near total thyroidectomy and I-131 treatments were included in this study. All 20 patients had negative I-131 WBS results and elevated hTg levels (hTg 2.0 microIU/ml) under thyroid-stimulating hormone (TSH) stimulation (TSH 30 microIU/ml). Nineteen of the 20 cases were confirmed to have metastases by operation/biopsy histopathological findings or clinical follow-up longer than 1 year by additional morphological imaging techniques. The remaining patient has been followed up closely and has been disease free for 10 months. Tc-99m TF SPECT was performed to detect metastatic lesions. RESULTS: Tc-99m TF SPECT demonstrated lesions in 11/19 patients; a sensitivity of 57.9%. Tc-99m TF SPECT failed to demonstrate lesions in eight patients including smaller lymph nodes and miliary lung metastases. CONCLUSIONS: We conclude that Tc-99m TF SPECT is a useful additional tool to detect metastatic lesions in PTC with elevated hTg but negative I-131 WBS. However, smaller lymph nodes and miliary lung metastases may be missed.     

Localization of human osteogenic sarcoma xenografts in nude mice by a monoclonal antibody labeled with radioiodine and indium-111

Monoclonal antibody OST7 reacts specifically with human osteogenic sarcoma. Whole immunoglobulin G (IgG) and the F(ab')2 fragment of OST7 were labeled with radioiodine and indium-111 (111I), and injected into athymic nude mice bearing xenografts of human osteogenic sarcoma (KT005). All radiolabels retained their antigen-binding activities allowing clear visualization of transplanted tumors. Tissue distribution, however, varied. The net tumor concentration of 111In-lableled whole IgG was higher and was retained longer than that of radioiodinated one, but 111In-labeled antibody showed a lower tumor-to-liver and tumor-to-kidney ratio. In radioiodinated OST7, F(ab')2 fragments provided much better images with much higher tumor-to-tissue ratios than whole IgG. Using F(ab')2 fragments as a carrier for 111In, little image improvement was obtained due to the high radioactivity in the liver and kidney. The different distributions among these radiolabels suggest that the choice between intact igG and F(ab')2 fragments and between radioiodine and 111In depends on the intended use.     

Positron emission tomography of the thyroid, with an emphasis on thyroid cancer

The role of Positron Emission Tomography (PET) using 18F-fluorodeoxyglucose (FDG) in the management of thyroid cancer is discussed. It is important to ensure that patients are relaxed because uptake of FDG in tense or active muscles in the neck and larynx can be misinterpreted as metastases. The major role for PET is in patients where the stage of disease is uncertain, usually the result of discordant negative 131I scan and a positive serum thyroglobulin (Tg) values. PET identifies the source of Tg production in 50-80% of patients. PET scan can be negative in well differentiated cancers which retain the ability to trap iodine. This can result in a 'flip/flop', with negative PET, positive radio-iodine scan, or positive PET, negative radioiodine scan. PET is also valuable in identifying the source of calcitonin production in patients with medullary thyroid cancer. When focal uptake is seen in the thyroid of patients who are scanned for non thyroidal reasons, the likelihood of primary thyroid cancer is high. In contrast diffuse uptake of FDG in the thyroid is usually the result of auto-immune thyroid disorders.     

异黄酮改构化合物F11对人乳腺癌裸鼠移植瘤的影响

目的研究异黄酮改构化合物F11对人乳腺癌裸鼠移植瘤影响。方法体外培养人乳腺癌MCF-7细胞，裸鼠皮下接种MCF-7细胞建立裸鼠移植瘤动物模型，用金雀异黄素（Genistein）和环磷酰胺为对照研究化合物F11在体抗MCF-7效应。结果通过裸鼠移植瘤模型检测，认为异黄酮改构化合物F11在体有显著的抗癌效应，效果优于Genistein。结论异黄酮改构化合物F11有较强的抑制肿瘤的作用，有值得进一步研究开发的潜在价值。     

Effect of glucose and confluency on phosphorus metabolites of perfused human prostatic adenocarcinoma cells as determined by31P MRS

A series of perfused cell³¹P MRS studies were conducted using a well established human prostate adenocarcinoma cell line (DU 145) at different phases of growth, and exposed to varying glucose concentrations during growth. The spectral characteristics of perfused DU 145 cells were compared with the same cells grown in nude mice (xenografts). Perfused DU 145 cells had lower levels of inorganic phosphate and phos-phocreative relative to in vivo nude mice xenografts. ³¹P MR spectra obtained from perfused cells at different phases of growth and exposed to varying glucose concentrations during grown suggest that increases in diphosphodiester levels are associated with high glucose concentrations and confluency. Perfused DU 145 cells grown in 5.5 mm glucose and harvested at log phase of growth best reflected the phosphorus MR spectra of the same cell line grown in nude mice.     

Visualization of the thymus with therapeutic doses of radioiodine in patients with thyroid cancer

Two cases of papillary carcinoma of the thyroid are presented in which whole-body scans following therapeutic doses of iodine-131 revealed intense anterior mediastinal uptake. In both cases, the mediastinal uptake was absent from scans obtained after removal of the entire thymus. Histologically, the resected thymus glands showed hyperplasia and contained neither thyroid tissue nor metastatic foci of thyroid carcinoma. We therefore concluded that anterior mediastinal uptake of radioiodine may be caused by hyperplasia of the thymus.     

Management of patients with thyroid carcinoma: application of thallium-201 scintigraphy and magnetic resonance imaging

Thyroid carcinoma has the ability to concentrate radioiodine, an attribute that can be used both for detection of thyroid cells and for treatment. Unfortunately, however, radioiodine uptake is not observed in all patients and a radioiodine scan requires that the patient be rendered hypothyroid for 4-6 wk. In the present study, we analyzed the utility of thallium-201 scanning and the usefulness of magnetic resonance imaging (MRI) in the detection of thyroid cancer. Nineteen patients with thyroid cancer had a total of 24 radioiodine scans, 33 thallium scans, and 10 MRI examinations. Of the 19 patients in the study, 17 had differentiated thyroid carcinoma. In these 17 cases, all paired studies were concordant for the presence (n = 7) or absence (n = 10) of disease. However, in one case (Patient 10), the 201Tl studies showed far more extensive disease than was observed on the 131I scan. Thyroid cancer was also detected on seven MRI studies. In summary, thallium and MRI scans are adjunctive techniques to radioiodine scanning that can either confirm the presence of neck bed activity, residual disease or metastatic cancer and may delineate tumor deposits not detected by radioiodine scanning. Thallium may be capable of detecting tumor deposits even while a patient remains euthyroid.     

Unusual widespread metastatic presentation of mixed medullary-follicular thyroid carcinoma

Mixed medullary-follicular thyroid carcinoma (MMFTC) is a rare tumor with a metastatic behavior that has not been fully appreciated. Scintigraphy and radioiodine entrapment propensity of its metastases remains largely undescribed. The authors present a case of MMFTC with widespread bone and soft-tissue metastases, where every known site of metastases concentrated radioiodine intensely. The patient responded well to radioiodine therapy. The report suggests that the tumor may have a propensity to metastasize to the skeleton, and the metastases retain the ability to accumulate radioiodine.     

PET in the follow-up of differentiated thyroid cancer

Fluorine-18-fluorodeoxyglucose (FDG) PET has become an increasingly important functional imaging modality in clinical oncology. This article will focus primarily on the role of FDG PET during treatment and follow-up of thyroid cancer. The major role of FDG PET is in patients with elevated thyroglobulin (Tg) levels where thyroid cancer tissue does not concentrate radioiodine rendering false-negative results on I-131 scanning. FDG PET imaging takes advantage of the increased uptake of FDG in cancer cells and is sensitive (60-94%) to the detection of recurrent or metastatic cancer in patients who have negative radioiodine scans. The specificity (25-90%) of PET imaging is relatively less than its sensitivity because some inflammatory processes avidly accumulate FDG. PET can fail to localize the tumour sites in some patients with well-differentiated thyroid cancer that retain good iodine ability. This can result the well recognized phenomenon of "flip-flop" depending on the differentiation of the thyroid cancer. Several studies have documented the higher accuracy of PET, compared with other imaging modalities in the evaluation of patients with recurrent or metastatic differentiated thyroid cancer. The value of thyroid stimulating hormone stimulation for FDG PET has recently been reported. Therefore, if available, this method should be considered in all patients of differentiated thyroid cancer with suspected recurrence and/or metastasis.     

维甲酸联合曲古抑素诱导及治疗荷人甲状腺滤泡状癌裸鼠的实验研究

目的探讨全反式维甲酸（ATRA）和曲古抑素（TSA）对人甲状腺滤泡状癌细胞株（FTC-133）和荷人甲状腺滤泡状癌裸鼠（NMB—hFTC）肿瘤模型摄碘能力的影响。方法不同量ATRA、TSA诱导VFC-133细胞：ARTA 1．0×10^-6mo／L（A低组）、1．0×10^-4mol／L（A高组）、TSA1．65×10^-7mol／L（T组）、A低＋T组、A高＋T组和无水乙醇（对照组）,96h后行HE染色,测定FTC-133细胞摄碘率;制备NMB—hFTC,成瘤后分组：ATRA组（2mg／kg灌胃）、TSA组（10mg／kg腹腔注射）、联合组（ATRA＋TSA,用量同前）、对照组（生理盐水灌胃＋腹腔注射,均为10ml／kg）,剂量均按鼠体质量给予。给药22d后,腹腔注射37MBq ^131I,分别于注射后4,6,12和24h行γ显像,测定体内生物分布;显像后取肿瘤组织行HE染色观察细胞形态。实验结果采用SPSS13．0软件进行单因素方差分析。结果FTC-133细胞摄碘率A低＋T组、A高＋T组分别为（23885±616．0）和（13849±728．2）计数·min^-1·10^-6细胞,其他各组在（985±84．2）～（17600±782．7）计数·min^-1·10^-6细胞范围内,各组间比较差异有统计学意义（F=600．879,P〈0．001）。^131I注射后6,12和24h联合组裸鼠种植瘤％ID／g分别为6．17±0．46,9．34±0．61,11．19±0．98,其余各组保持在（1．97±0．34）～（5．14±0．65）之间;肿瘤质量各组间比较差异有统计学意义（F=3．723,P〈0．05）。结论ATRA联合TSA,可增强FTC-133细胞和NMB—hFTC病灶的分化、摄碘能力,达到增强^131I杀死甲状腺癌病灶的协同作用。     

甲状腺癌术后131I首次清除剩余甲状腺疗效分析

目的　观察不同年龄、性别、病理类型、手术方式、术后13 1I治疗时间、13 1I剂量、TSH水平以及剩余甲状腺外转移灶是否同时摄碘等因素对分化型甲状腺癌术后患者首次13 1I清除剩余甲状腺的影响。方法　分化型甲状腺癌术后患者 85例 ,手术治疗后 ,口服13 1I 1.11～ 5 .5 5GBq进行首次13 1I治疗 ,3～ 6个月后随访 ,以颈部剩余甲状腺显像与周围本底相比未见摄碘为成功清除的标准。结果85例中成功者 5 8例 ,成功率 6 8.2 %。不同的13 1I剂量、手术方式、术后首次治疗时间、TSH水平的变化以及剩余甲状腺外转移灶是否同时摄碘分别与成功率有一定关系 ;其中术后首次治疗时间与成功率之间呈负相关 (r=- 1.10 84,r0 .0 1( 3 ) =0 .95 9,P <0 .0 1)。不同年龄、性别及病理类型与成功率之间无明显关系。结论　适当的13 1I剂量、甲状腺全切手术、术后首次13 1I治疗时间 3个月以内、5 0mU/L以上的TSH水平以及仅有剩余甲状腺摄碘的分化型甲状腺癌术后患者疗效较好。疗效与患者的年龄、性别及病理类型无关     

The effect of gadolinium contrast media on radioiodine uptake by the thyroid gland

OBJECTIVE: Patients with thyroid cancer may require detailed anatomic imaging before 131I therapy. Imaging by contrast-enhanced CT is contraindicated because it may result in saturation of tissues with iodine, decreasing the avidity of thyroid or thyroid cancer cells to subsequent radioiodine for extended intervals. Gadolinium-enhanced MRI offers an alternative to CT for detailed anatomic imaging. However, it is not known whether gadolinium contrast affects uptake of iodine by the thyroid gland since lanthanides affect ion transport in a variety of ways. The objective of this project was to determine whether the gadolinium MRI contrast injection alters thyroid uptake of radioiodine. METHODS: Radioiodine uptake by the thyroid gland was measured at 6 h and 24 h after the oral administration of 100 microCi 123I-Na-I. Three to seven days later, a standard dose (20 mL) of Magnevist (gadolinium DTPA) was administered intravenously. Another capsule of 100 microCi 123I Na-I immediately was given orally, and 6-h and 24-h radioiodine uptake by the thyroid gland was again measured and compared to baseline values. RESULTS: There was no statistically significant difference in uptake of radioiodine uptake by the thyroid gland between baseline values and those acquired immediately after the administration of Magnevist. CONCLUSION: Contrast-enhanced MRI may be safely performed before contemplated determinations of thyroid uptake of radioiodine, 131I therapy for hyperthyroidism, and postsurgical 131I imaging and therapy for well-differentiated thyroid cancer.     

CD/5-FC自杀基因系统治疗胰腺癌的实验研究

为探讨自杀基因CD/5-FC系统对胰腺癌的杀伤作用及作用机制,应用细菌内同源重组法构建含大肠杆菌胞嘧啶脱氨酶（cytosine deaminase, CD）基因的腺病毒载体,经293细胞包装、扩增,氯化铯密度梯度离心制备纯化CD腺病毒液,体外转染人胰腺癌细胞,并给予前药5-FC,观察其体外杀伤效果;并建立胰腺癌裸鼠皮下移植瘤模型,瘤内直接注入CD腺病毒液,随后腹腔内注入5-FC,观察CD基因的原位治疗效应。含CD基因腺病毒载体经酶切鉴定正确,包装纯化后,检测病毒滴度为2×1011pfu/ml,将重组腺病毒转染胰腺癌细胞株后,可见5-FC对转导入CD基因的胰腺癌细胞有明显细胞毒性作用,而对未导入CD基因的人胰腺癌细胞毒性较低,体内实验显示CD基因原位转导对裸鼠胰腺癌疗效较明显。腺病毒介导CD基因,不仅转染效果强,而且加用5-FC后,可直接或通过旁观者效应杀伤胰腺癌细胞或抑制移植瘤的生长,可作为胰腺癌基因治疗的有效方法。