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Objective To observe the hematological toxicity of 89SrCl2 in patients with multiple bone metastases of malignant tumors,and analyze the related-risk factors.Methods A total of 89 patients (63 males,26 females;age:(62.3±5.2) years) with multiple bone metastases and treated with 89SrCl2 were enrolled.Hematological data at 2 and 4 weeks after treatment with 89SrCl2 were analyzed.Common Terminology Criteria for Adverse Events (CTCAE) v4.03 was used to evaluate the hematological toxicity,and the influencing risk factors were analyzed.Logistic regression analysis was used to analyze the data.Results The incidences of grade Ⅰ-Ⅱ anemia,leukopenia and thrombocytopania at 2 and 4 weeks after treatment were 15.7％(14/89),18.0％(16/89),11.2％(10/89) and 18.0％(16/89),24.7％(22/89),18.0％(16/89),respectively.The incidences of grade Ⅲ-Ⅳ anemia,leukopenia and thrombocytopenia were 2.2％(2/89),0,0 and 2.2％(2/89),2.2％(2/89),3.4％％(3/89),respectively.Logistics multivariate analysis showed that the number of bone metastases and the Hb level before treatment were independent effect factors for hematological toxicity of 89SrCl2,with odds ratio (OR) values of 2.200(95％ CI:1.269-3.841) and 0.961 (95％ CI:0.932-0.991),respectively.Conclusions Serious hematological toxicity after 89SrCl2 treatment is rare.The number of bone metastases and the Hb level before treatment are independent effect factors for hematological toxicity.
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The clinical nuclear medicine can be used for disease diagnosis and treatment,however,in the diagnosis and treatment process,the patient becomes a source of radiation not only to him/herself,but also to the general public and medical staff,which has been a topical subject with the public awareness of radiation protection gradually.How we scientifically regard the radiation will help promote the development of nuclear medicine,and eliminate the fear of the public.The radiation protection and safety is an important part of clinical nuclear medicine and the development of fine disciplines.The new ideas and knowledge about radiation protection and safety of patients,public and nuclear medical staff in recent years were reviewed in this article.
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Objective To evaluate the efficacy and safety of 13-cis retinoid acid (13-CRA) and all trans retinoid acid (ATAR) redifferentiation therapy in patients with poorly differentiated thyroid cancer. Methods A single-center, randomized, double-blind, parallel controlled clinical trial was preformed. All patients were randomized into three groups. 78 cases were enrolled in each group. The patients were treated by 13-CRA in A group, by ATRA in B group, and by placebo in control group. The induced effects of retinoid acid (RA) and 131I treatment efficacies were defined as primary outcome of efficacy. Results After RA induction therapy, the effective rates in A, B, and control groups were 59.72%, 52.86% and 7.69%, respectively, with statistically significant difference among 3 groups (P<0.05). Compared with control group, A and B groups revealed significant induced efficacies (P<0.017), but there was no significant difference between A group and B group. After 131I treatment, the effective rates in A, B, and control group were 70.83%, 64.29%, and 28.21% respectively, with statistically significant difference (P<0.05). Compared with control group, the effective rates of 131I treatment in A and B groups were significantly raised (P<0.017), but there was no significant difference between A group and B group. The damage of skins and mucous membranes such as desquamation, dry skin, dry lips, dry eyes, etc occurred mostly in A group. The symptoms of nervous system such as headache, dizziness, etc occurred mostly in B group. Conclusions The induced differentiation of 13-CRA or ATRA is an effective method for the treatment of poorly differentiated thyroid carcinoma.
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Objective To investigate the biokinetics of 131 I and its absorbed dose in patients with metastatic DTC. Methods Forty?one patients with metastatic DTC who were referred to 131 I therapy were prospectively recruited from September 2009 to September 2011. Scintigraphic images were serially acquired after the ingestion of 131I (3.70-9.25 GBq) to assess the biokinetics. CT was used to measure the masses of the DTC lesions. Calculation of absorbed doses to DTC lesions was based on the Medical Internal Radiation Dosimetry formula of the Society of Nuclear Medicine and Molecular Imaging. Kruskal?Wallis rank sum test was used to compare the differences of absorbed dose among different tumor deposits. Results In total, 59 io?dine?avid metastatic lesions (35 in cervical lymph node, 17 in lung and 7 in bone) in 41 patients were evalu?ated and the mean absorbed dose of DTC lesions was (10.4±6.5) Gy/GBq, with range of 0.1 to 136.2 Gy/GBq. The median absorbed dose was 11.3 Gy/GBq for lymph node metastase, 10.1 Gy/GBq for lung metastases and 9.6 Gy/GBq for bone metastases. There were no statistically significant differences in absorbed doses a?mong the metastases of lymph node, lung and bone ( Z=0.907, P>0.05) . Conclusion A wide inter?lesion variation of absorbed dose to metastatic DTC is observed.
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Diagnostic whole body scan (Dx-WBS) with 131I and serum Tg level are the main parameters to evaluate the effectiveness of thyroid remnant ablation in patients with DTC.Undetectable Tg and positive radioiodine uptake in the thyroid bed (Tg-/Dx-WBS+) may be found in some patients.However,the clinical significance is uncertain.A small amount of thyroidal remnant,a small DTC lesion,increased expression of NIS gene and autoimmune inflammation may all result in Tg-/Dx-WBS+.A wait-and-watch approach without rushing for high-dose radioiodine treatment might be a more reasonable approach for these patients.
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Positron emission tomography (PET) is a highly sensitive and low invasive technology for cancer biological imaging. Integrated PET/computed tomography (PET/CT) cameras combine functional and anatomical information in a synergistic manner that improves diagnostic interpretation. The role of 18F FDG PET/CT in differentiated thyroid cancer (DTC) is well established, particularly in patients presenting with elevated thyroglobulin (Tg) levels and negative radioactive iodine scan. This review presents the evidence supporting the use of 18F FDG PET/CT throughout the diagnosis and management of thyroid cancer, and provides suggestions for its clinical uses.
Subject(s)
Humans , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Thyroglobulin , Blood , Thyroid Neoplasms , Diagnosis , Tomography, X-Ray ComputedABSTRACT
According to the inclusion and exclusion criteria, we searched for relevant original articles in some big Chinese and English databases. The qualities of the studies were evaluated with QUADAS quality assessment tool. A software program, Meta-disc, was used to obtain the pooled estimates and heterogeneity test for sensitivity, specificity, SROC curve, and so on. Finally the 17 article were included. On a per-patient basis, the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), Q*, SROC area under curve for 99mTc-MDP bone scan and computed tomography (CT) were 0. 87 and 0.99, 0.81 and 0.98, 3.88 and 13.86, 0.2 and 0.03, 27.73 and 612.17, 0.8418 and 0.9732, 0.9097 and 0.9952, respectively. On a per-focus basis, the pooled SEN, SPE, LR+, LR-, DOR, Q*, SROC area under curve for 99mTc-MDP bone scan was 0.86, 0.97, 13.32, 0.16, 102.4, 0.8944, 0.9528, respectively. For CT, only 1 article were included. This paper demonstrate: whether 99mTc-MDP or CT both have high diagnostic efficiency for bone metastase of breast cancer.
Subject(s)
Female , Humans , Bone Neoplasms , Diagnosis , Breast Neoplasms , Pathology , Sensitivity and Specificity , Technetium Tc 99m Medronate , Tomography, X-Ray ComputedABSTRACT
For patients with DTC,the side effect of 131I therapy on fertility and offspring is an important issue since genital tissues are highly sensitive to radiation.Exposure to 131 I radiation may result in transient impairment of gonadal function in male patients caused by elevated levels of serum follicle stimulating hormone and luteinizing hormone,low sperm count and motility.In female patients,exposure to 131I radiation may be complicated with delay of menstruation,oligomenorrhea and transient cessation of menstrual period.Most of these symptoms may resolve within one year after 131 I therapy.A slightly earlier menopause is the only reported long-term side effect of 131I therapy on ovarian function.Currently available data do not indicate that exposure to 131I may cause permanent infertility in male patients with DTC.For female patients with DTC,131 I therapy does not affect fertility or pregnancy outcomes beyond one year.
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Objective To investigate the relationship between the absorbed dose to the thyroid remnant and the outcome of m I ablation in patients after operation for DTC.Methods Seventy-two patients (14 males,58 females; age range:16-67 years,average age:(41±16) years) with DTC,prepared for thyroid remnant ablation,were prospectively recruited from September 2009 to September 2011.Scintigraphic images of the head and neck were serially acquired after oral administration of 3.7 GBq of 131I to assess the biokinetics of this tracer in thyroid remnant.Ultrasound was used to measure the mass of the thyroid remnant.Calculation of absorbed dose to thyroid remnant was based on the Medical Internal Radiation Dosimetry formula of the Society of Nuclear Medicine.The outcome of 131 I ablation was evaluated on the basis of stimulated Tg measurements and neck ultrasound at 6-9 months after ablation.Patients with stimulated Tg levels less than 1 μg/L and with no detectable thyroid tissue on neck ultrasound were considered successful ablation of thyroid remnant.Two-sample t test was used to analyze the data.Results The 131I uptake ratios at 24 h were 0.9％-6.3％ in 72 patients and the effective half-lives of 131I were 12.0-146.4 h.The thyroid remnant masses were 1.0-6.9 g; absorbed doses were 23-2 197 Gy,and absorbed dose rates at 24 h were 0.5-8.1 Gy/h.No significant difference was observed in absorbed doses to thyroid remnants in 43 patients having successful ablation and 29 patients having unsuccessful ablation ((363± 148) Gy vs (341± 167) Gy,t =15.097,P＞0.05).However,the absorbed dose-rates of thyroid remnants at 24 h were significantly higher in patients with successful ablation than those in patients with unsuccessful ablation ((3.7±2.1) Gy/h vs (2.9±1.6) Gy/h,t=7.908,P＜0.05).Conclusion A successful ablation is strongly dependent on the absorbed dose-rate of thyroid remnant.
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Smac is a mitochondrial protein that interacts with inhibitor of apoptosis proteins (IAPs). Upon apoptotic stimuli, the Smac is released into the cytoplasm to inhibit the capase-binding activity of IAPs. The low expression of Smac in tissues has been reported existing in various cancers. Smac plays key roles in prognosis and chemoradiotherapy resistance of malignant tumor besides neoplasm genesis and growth. Furthermore, Smac may be a molecular therapeutic target in cancer patients. Overexpression of Smac by transfecting extrinsic Smac gene or Smac mimetic into tumor cell can improve their sensitivity to radiotherapy and chemotherapy, which has great significance to the treatment of tumor. Our review will focus on the roles of Smac in structure, pro-apoptotic mechanism, tissue distribution and cancer treatment.
Subject(s)
Humans , Intracellular Signaling Peptides and Proteins , Chemistry , Metabolism , Physiology , Mitochondrial Proteins , Chemistry , Metabolism , Physiology , Neoplasms , Therapeutics , Tissue DistributionABSTRACT
Traditionally, during the follow-up and in order to receive 131 I therapy, patients with differentiated thyroid carcinoma (DTC) have to withdraw from using thyroid hormone. The hypothyroidism induced by hormone withdrawal can negatively affect the quality-of-life (QOL) of DTC patients. Without the hormone withdrawal, recombinant human thyroid-stimulating hormone-aided management of DTC patients can effectively obviate the consequences of hypothyroidism. This review will focus on the clinical application of recombinant human thyroid-stimulating hormone (rhTSH) in the management of DTC patients.
Subject(s)
Humans , Iodine Radioisotopes , Therapeutic Uses , Thyroglobulin , Blood , Thyroid Hormones , Thyroid Neoplasms , Blood , Drug Therapy , Radiotherapy , Thyrotropin AlfaABSTRACT
The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and phoshoinositide-3-kinase/protein kinase B (PI3K/Akt) signaling pathways play a major role in regulating cell growth, proliferation and apoptosis, via transmission of cell signals to cell nucleus. The genes, coding the MAPK/ERK and PI3K/Akt signaling cascade proteins, are significantly mutated in thyroid cancer. Genetic alternations contribute to aberrant activations and interaction of MAPK/ERK and PI3K/Akt signaling pathways in consequence of malignant follicular cell transformation and progression. This review focuses mainly on the role of genetic alterations in coding MAPK/ERK and PI3K/Akt signaling pathway proteins in generation, progression and diagnosis of thyroid cancer. Moreover, it additionally points out a therapeutic potential in restoring iodine avidity of thyroid cancer cells for radionuclide targeted treatment, by synergistically inhibiting activity of signaling pathways.
Subject(s)
Humans , Extracellular Signal-Regulated MAP Kinases , Genetics , Metabolism , MAP Kinase Signaling System , Genetics , Mitogen-Activated Protein Kinases , Genetics , Metabolism , Mutation , Phosphatidylinositol 3-Kinases , Genetics , Metabolism , Proto-Oncogene Proteins c-akt , Genetics , Metabolism , Signal Transduction , Genetics , Physiology , Thyroid Neoplasms , Genetics , TherapeuticsABSTRACT
This paper is aimed to evaluatethe thyroglobulin autoantibody (TgAb) interference in measurement of thyroglobulin (Tg) between electrochemiluminescent assay (ECLIA) and radioimmunoassay (RIA). Tg and TgAb of 84 sera, including 22 Graves' hyperthyroidism(GD), 24 Hashimoto thyroiditis (HT) and 38 differentiated thyroid carcinomas (DTC), were measured by RIA and ECLIA, respectively. Recovery tests were carried out in 3 groups. The sera samples of the first group were added 3 different amount of Tg calibrator; the sera samples of the second group were diluted 5 times, then 100 ng/ml Tg calibrator was added; the sera samples of the third group were divided into different subgroups depending on TgAb concentration with adding 100 ng/ml Tg calibrator,Tg and TgAb were measured in each dilution by ECLIA and RIA. Recovery rate was calculated. The Tg and TgAb values measured by ECLIA were correlated with that measured by RIA (r = 0.676, P = 0.000; r = 0.677, P = 0.000, respectively). When TgAb concentration increased, the Tg values decreased by ECLIA and increased by RIA. The TgAb values were decreased when sera were diluted, and the Tg values also reduced by RIA and increased by ECLIA. The added different amount of Tg calibrator had not significant influence on Tg recovery rates. When TgAb concentration increased, recovery rates of Tg were decreased by ECLIA and increased by RIA. When sera were diluted, the recovery rates of Tg were increased by ECLIA while decreased by RIA. RIA and ECLIA have good correlation with Tg measurement in 10-400 ng/ml. ECLIA has wider measuring range and higher sensitivity than RIA. RIA and ECLIA have good correlation with TgAb measurement. When TgAb is positive, Tg values are underestimated by ECLIA and overestimated by RIA. When sera are diluted, Tg value and the recovery rate are increasing by ECLIA and decreased by RIA. Recovery test can not efficiently rectify Tg value when TgAb is positive.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Autoantibodies , Blood , Electrochemical Techniques , Graves Disease , Blood , Hashimoto Disease , Blood , Luminescent Measurements , Methods , Radioimmunoassay , Methods , Thyroglobulin , Blood , Allergy and Immunology , Thyroid Neoplasms , BloodABSTRACT
This paper was aimed to investigate the biodistribution and ability of free 131-bcl-2/bcl-xl ASON (FA) and anionic long circulation liposomes encapsulated with 131I-bcl-2/bcl-xlASON (NA), in tumor-bearing rats, to image breast cancer. We investigated the tissue distribution of NA in virgin female Sprague-Dawley (SD) rats with n-methyl nitrosourea (MNU)-induced breast cancers in situ. The percentage of the injected dose per gram (%ID/g) was calculated, with the maximum ratios of tumor to blood and tumor to muscle, after injections of NA and FA for 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 12 h and 24 h, respectively. The ability of NA to image breast cancer in tumor-bearing rats was determined using emission computed tomography (ECT). Seventy percent (90/130) SD rats in the study developed mammary tumors after MNU injection with the average latency (NA) (96 +/- 1.2)days. The %ID/g of NA in breast cancer tissue, tumor bearing rats in liver and spleen tumor tissues after 10 hours were (6.23 +/- 0.23) %ID/g, (12.00 +/- 0.26) %ID/g and (18.25 +/- 1.33)% ID/g, respectively. The ratios of tumor to blood 6.29 +/- 0.76 and tumor to muscle 10.55 +/- 0.68 in tumor bearing rats slowly maximized at 10 h post injection of NA, most probably due to the enhanced permeability and retention effect. Hence in radionuclide antisense scintigraphy, the breast cancer in rat was clearly displayed at 10h after iv administration of NA-D. However, tumors were not visualized in rats with the iv injection of NS and NN even at the delayed time. Due to the inhibition of rapid uptake of NA by the reticulo-endothelial system, NA displays valuable pharmacologic properties characterized by the enhanced accumulation in tumor.
Subject(s)
Animals , Female , Rats , Iodine Radioisotopes , Liposomes , Pharmacokinetics , Mammary Neoplasms, Experimental , Metabolism , Oligonucleotides, Antisense , Pharmacokinetics , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Radionuclide Imaging , Methods , Random Allocation , Rats, Sprague-Dawley , Tissue Distribution , bcl-X Protein , MetabolismABSTRACT
Serum thyroglobulin (Tg) is primarily used as a tumor marker to detect the recurrent or persistent disease in patients with differentiated thyroid carcinomas. Unfortunately, the serum Tg measurement is technically challenging and the thyroglobulin autoantibody (TgAb) interference remain the most serious problem limiting the clinical value of serum Tg. The direction and magnitude of the interference are related to the method and the concentration and affinity of the TgAb in the specimen. The objective of this study was to evaluate TgAb's interference with assay of Tg by electrochemiluminescent assay (ECLIA). The Tg and TgAb of 84 sera were measured by the ECLIA. Recovery tests were carried out in 3 groups. 3 different Tg calibrators, 50, 100, 200 ng/ml, respectively, were added into the sera of the first group. The sera of second group were doubly diluted 5 times, and meawhile the Tg and TgAb were measured after each dilution, and then 100 ng/ml Tg calibrator was added into the sera. The sera of third group were divided into different subgroups according to TgAb concentration and then 100 ng/ml Tg calibrators were added. Recovery rate (%) was calculated. Tg value decreased when TgAb concentration increased by ECLIA, TgAb value became lower when sera were diluted, Tg value increased. The added Tg calibrator had not significant influence on Tg value and Recovery rate. Recovery rate was lower when TgAb concentration increased. When sera were diluted, the recovery rate was increased. Tg value were underestimated by TgAb interference. After sera were diluted, Tg value became increasing by ECLIA. The added Tg calibrator had not significantly influence on Tg value and Recovery rate. When sera were diluted, the recovery rate was increased. TgAb concentration had significant influence on Recovery rate. Recovery test can not efficiently rectify Tg value when TgAb was positive.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Autoantibodies , Blood , Allergy and Immunology , Electrochemical Techniques , False Positive Reactions , Graves Disease , Blood , Hashimoto Disease , Blood , Luminescent Measurements , Methods , Thyroglobulin , Blood , Allergy and ImmunologyABSTRACT
The objective of this work was to observe the side effects on the peripheral blood treated with 131I in children and adolescents with differentiated thyroid carcinoma (DTC). The levels of white blood cells (WBC), neutrophil, HGB (hemoglobin), RBC (red blood cells) and the PLT (platelet) were measured by automatic hemocyte analyzer in 31 young enrolled patients (< or = 20 years old) before 131I therapy, 1 month and 6 months after 131I therapy, and at the end of follow up. The results of 131I treatment at the before and after the treatment were compared. The level of PLT decreased obviously (P < 0.01), WBC, RBC and HGB decreased (P < 0.05), neutrophil increased slightly (P > 0.05) 1 month after 131I therapy. The level of WBC, neutrophil, RBC, HGB and PLT were near to the level of before treatment after 6 months (P > 0.05) of 131I therapy. At the end of follow up, the components of the peripheral blood in the high dose group (7.4GBq-11.1GBq) were not significantly different from those at the beginning. The results showed that, there was only a transient impact on the peripheral blood by the 131I therapy in the children and adolescents with differentiated thyroid carcinoma.
Subject(s)
Adolescent , Female , Humans , Male , Young Adult , Blood Cell Count , Carcinoma , Blood , Radiotherapy , Iodine Radioisotopes , Therapeutic Uses , Thyroid Neoplasms , Blood , RadiotherapyABSTRACT
The objective of this work was to estimate the absorbed dose of 131I to lungs in 131I therapy of differentiated thyroid carcinoma(DTC) with diffuse pulmonary metastases. Ten DTC patients with diffuse pulmonary metastases were recruited prospectively. Whole body planar scintigrams were acquired serially after administration of 7.4 GBq 131I to patients. The counts from the regions of interest of lungs and total body were obtained and converted to the percent of administered activity. The time-activity curves of lungs and total body were fit, and the areas under the curves were calculated. It was assumed that beta-eletron emissions from 131I deposited in lungs were completely absorbed by the diffuse DTC metastatic lesions, and that gamma-photon emissions from 131I deposited in the lungs and the remainder of body were irradiating the lungs. The absorbed dose to lungs was calculated according to Medical Internal Radiation Dosimetry (MIRD) formula. The median lungs absorbed dose was 0.33 Gy (range, 0.22-8.21 Gy). Based on the empiric fixed activity therapy of DTC with diffuse pulmonary metastases,the absorbed dose to lungs is low.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma , Pathology , Radiotherapy , Iodine Radioisotopes , Pharmacokinetics , Therapeutic Uses , Lung , Metabolism , Lung Neoplasms , Radiotherapy , Radiotherapy Dosage , Thyroid Neoplasms , Pathology , RadiotherapyABSTRACT
Treatment of differentiated thyroid carcinoma (DTC) with ~(131)Ⅰ can greatly improve prognosis of patients. However, the administered activity of ~(131)Ⅰ is still a subject for discussion. Different methods for determining the administered activity of ~(131)Ⅰ were reviewed in this article.
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This study sought to probe the feasibility of instituting a radioiodide treatment for androgen-independent prostate cancer by adenovirus transfer of the hNIS gene. A recombinant adenovirus, Ad-CMV-NIS, that expressed the NIS gene under the control of cytomegalovirus (CMV) promoter was constructed. In vitro, after infection with Ad-CMV-NIS,PC-3 prostate cancer cells exhibited an uptake of perchlorate-sensitive iodide, approximately 120 times higher than that exhibited by negative control Ad-CMV-GFP-infected cells. The half-time of efflux was 26.6 min. Clonogenic assays demonstrated that Ad-CMV-NIS-infected cancer cells were selectively killed by exposure to 131I. In vivo, Ad-CMV-NIS infected tumors showed significant radioiodine accumulation (16.30 +/- 8.72)% ID/g at 2h postinjection) with an effective half-life of 5.4h. The tumor could be clearly visualized by 131I scintigraphy. These data indicate that infection with Ad-CMV-NIS is an efficient way to induce radioiodide uptake in vitro and in vivo, thus suggesting that NIS-based gene therapy has the potential for use in androgen-independent prostate cancer.
Subject(s)
Humans , Male , Adenoviridae , Genetics , Metabolism , Genetic Therapy , Methods , Iodine Radioisotopes , Therapeutic Uses , Prostatic Neoplasms , Genetics , Metabolism , Radiotherapy , Symporters , Genetics , Transfection , MethodsABSTRACT
Radioiodine therapy of carcinoma could be mediated by transferring the genes which participate in the process of iodine metabolism in thyroid. The correlative genes are sodium/iodine symporter gene, thyroid peroxidase gene and the specific thyroid transcription factors, and others. The objective gene can specifically express in carcinoma by inserting the tissue-specific promoter/enhancer upstream of them, so radioiodine could be used to treat varied carcinomas. The radioiodine uptake in carcinoma cells was obviously increased and the radioiodine therapy of carcinoma was effective after those genes had expressed in carcinoma cells. The main problem was that the effective half-time of radioiodine in cells was too short to produce the ideal effect of radioiodine therapy. Moreover, 211At and 188Re could be transferred by sodium/iodine symporter and they could be used to treat the carcinoma that is capable of radioiodine uptake.