Sufficiency of a Single Negative Thyroglobulin Standard for Judging the Success of Ablation in Low- and Intermediate-risk Differentiated Thyroid Cancer: A Retrospective Study.

BACKGROUND: We investigated how reduced successful ablation criteria may be used to evaluate radioiodine remnant ablation in patients with low- and intermediate-differentiated thyroid carcinoma (DTC). METHODS: Overall, 254 low- and intermediate-risk patients with DTC were categorized into three groups (positive, weak, positive, and negative) on the basis of a visual study of thyroid imaging performed before postoperative iodine treatment. Semi-quantitative analysis parameters were incorporated into the positive Tc-99m pertechnetate scanning to further examine the clinical use of thyroid imaging. We investigated the value of successful judgment criteria and the influencing factors of radioiodine ablation. At the same time, the predictive value of thyroglobulin (Tg) for radioiodine treatment and the overall clinical efficacy were assessed. RESULTS: A total of 250 (98.43%) patients were identified as having functional thyroid tissue residue on the Tx-whole-body scan, and 137 (53.94%) patients had positive Tc-99m pertechnetate scans using semi-quantitative analysis. The single Tg standard could not substitute the double standard (χ! !=22.042, p<0.001) for patients with residual thyroid weight by a semiquantitative analysis. However, the semi-quantitative analysis revealed no association between 99mTcO4-thyroid scan and ablation treatment using semi-quantitative analysis; only preablation sTg levels were related with success in the multivariate logistic regression analysis, with a cut-off value of 2.88 ng/mL. The pre-ablation stimulated Tg level was also the primary factor of satisfactory response following follow-up with an optimal cut-off of 6.506 ng/mL. CONCLUSION: Even in low- and intermediate-risk patients with DTC, a single negative Tg standard also requires receiving some restrictions in the evaluation of ablation success and is inadequate. Conventional 99mTcO4 thyroid imaging combined with a quantitative analysis program can improve the clinical practice of single negative Tg standard.

RADIOACTIVE IODINE THERAPY WITHOUT RECENT ANTITHYROID DRUG PRETREATMENT FOR HYPERTHYROIDISM COMPLICATED BY SEVERE HYPERBILIRUBINEMIA DUE TO HEPATIC DYSFUNCTION: EXPERIENCE OF A CHINESE MEDICAL CENTER.

OBJECTIVE: The objective of this work is to report our experience with (131)I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction. METHODS: Five patients with refractory severe hyperthyroidism were treated with (131)I at 90 to 120 µCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before (131)I treatment due to treatment failure or severe jaundice. Prior to (131)I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their (131)I treatment. The patients were followed for 4 to 9 years after (131)I therapy. RESULTS: After (131)I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after (131)I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy. CONCLUSION: (131)I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.

131I therapy for 345 patients with refractory severe hyperthyroidism: Without antithyroid drug pretreatment.

The aim of this study is to evaluate the safety and long-term results of (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment. From January 2002 to December 2012, 408 patients with refractory severe hyperthyroidism were treated with (131)I alone. Among them, 345 were followed up for 1 to 10 years for physical examination, thyroid function, and thyroid ultrasound. Complete Blood Count (CBC) liver function, electrocardiogram, echocardiogram, and Emission Computed Tomography (ECT) thyroid imaging were performed as indicated. The 345 patients had concomitant conditions including thyrotoxic heart disease, severe liver dysfunction, enlarged thyroid weighing 80 to 400 g, severe cytopenia, and vasculitis. One to two weeks prior to (131)I therapy, all patients were given low-iodine diet. The dose of (131)I therapy was 2.59 to 6.66 MBq (70 to180 µCi) per gram of thyroid with an average of 3.83 ± 0.6 MBq (103.6 ± 16.4 µCi); and the total (131)I activity administrated for the individuals was 111 to 3507.6 MBq (3.0 to 94.8 mCi, mean 444 ± 336.7 MBq (12.0 ± 9.1 mCi)). Out of the 408 patients, 283 were cured, 15 with complete remission, and 47 with incomplete remission. No treatment failure or significant clinical worsening was noted in these patients. Our data indicated that (131)I therapy alone for patients with refractory severe hyperthyroidism without antithyroid drug pretreatment is safe and effective.

[Antitumor effects of radioiodine labeled KH901 on nude mice bearing hepatoma].

In order to evaluate the biological activity in vitro and the antitumor effects of 131I-conditionally replicating oncolytic adenovirus KH901 on HepG2 human hepatoma xenografts, the leves of GM-CSF expression were determined by ELISA method. A panel of tumor and normal cells was infected with recombinant adenovirus KH901 at MOI of 10 PPC. The medium was harvested to determine the bioactivity of GM-CSF after 24 hours. Nude mice bearing HepG2 human hepatoma xenografts were given 131-KH901. Antitumor effects were assessed using endpoints of tumor growth delay. The data showed that after 24 hours 131-KH901 replicated hugely in tumor cells and produced significant amount of GM-CSF 183.27 +/- 6.90 pg/ml, while producing very small amount of GM-CSF 20.44 +/- 0.77 pg/ml in normal cells. In the treatment of tumor, 131I-KH901 showed higher restraint rate (71.3%) compared to 131I (22.7%) or KH901 (52.7%). Therefore, 131-KH901 can inhibit the growth of human hepatoma cell in nude mice and it may be a potential drug for treating liver cancer.

Imaging of radioiodine-labeled KH901, a tumor-specific oncolytic recombinant adenovirus, in nude mice with human hepatocellular carcinoma.

OBJECTIVE: To study the biodistribution and imaging of I/I-labeled KH901, a tumor-specific oncolytic recombinant adenovirus, in nude mice bearing human hepatocarcinoma. METHODS: KH901 was labeled with I/I according to the N-bromosuccinimide labeling method. The activity of granulocyte-macrophage colony-stimulating factor was determined by enzyme-linked immunosorbent assay. After I-KH901 was injected into the tumor, the label was followed in different organs and tumor tissues in nude mice with hepatocellular carcinoma. I-KH901 was injected directly into the tumor of nude mice bearing hepatocellular carcinoma, and their concentrations were detected at different times on radionuclide images. RESULTS: The radiochemical purity of I/I-KH901 was over 95%. I-KH901 stimulated massive expression of granulocyte-macrophage colony-stimulating factor in tumor cells. Twenty-four hours after the addition of I-KH901, the concentrations of granulocyte-macrophage colony-stimulating factor were 183.27+/-6.90 and 20.44+/-0.77 pg/ml in tumor and normal cells, respectively. I-KH901 was mainly distributed in the tumor and had a longer retention time, which was 14.93%ID/g at 24 h. Radionuclide imaging showed that the radioactive retention of I-KH901 in the tumor was significant. The tumor was shown clearly in the whole-body scan at 2 h after injection. CONCLUSION: I or I-KH901 concentrates specifically at the tumor site, which makes it a novel drug (combination of oncolytic adenovirus and radionuclide therapies) for the treatment of cancer.

[Effect of 131I-labeled recombinant human tumor necrosis factor-alpha on the nude mice bearing human hepatoma].

OBJECTIVE: To test the effect of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) labeled with 131I on tumor growth in the nude mice bearing human hepatoma. METHODS: The biological activity of 131I-rhTNF-alpha was tested through in vitro combination of the radioactive drug and SMMC-7721 cells. The BALB/c-nu/ nu mice model bearing human hepatoma were established by injecting single cell suspension of SMMC-7721 cells. When the tumor was 1 cm in diameter, the therapeutic experiment was carried out. Twenty-four nude mice bearing human hepatoma were divided into six groups according the area of tumor, weight and sex of the nude mice. After i. v administration of 131I-rhTNF-alpha, the body biodistribution of 131I-rhTNF-alpha was assessed during a short-term (30 min, 1 h, 6 h) and a long-term (12 h, 24 h, 48 h) period. The biological activity and tumor accumulation of 131I-rhTNF-alpha were investigated. In the end of the experiment, histopathologic examinations of tumor samples were undertaken. RESULTS: The combination of 131I-rhTNF-alpha with the human hepatoma SMMC-7721 cells existed dose dependence and saturability. The 131I-rhTNF-alpha had satisfactory immunoreactivity. The 131I-rhTNF-alpha accumulated in tumor tissues well and kept stable for several days. The tumor tissues accumulated the highest radioactivity at 6 h, and still maintained 67.5% of that radioactivity at 48 h. The 131I-rhTNF-alpha administrated either intravenously or intratumorally could inhibit tumor growth. The 131I-rhTNF-alpha had similar radioactivity as the positive control (P>0.05), but greater radioactivity than the control groups including 131I, rhTNF-alpha and the negative groups (P<0.05). CONCLUSION: The radioactive compound of 131I-rhTNF-alpha can inhibit and kill tumor cells, which demonstrates its potential for treating hepatocarcinoma.

[Iodination conditions of KH901, a tumor-specific oncolytic recombinant adenovirus, and its 125I-labeled compounds biodistribution in animals].

In this research was developed high efficiency method using 125I for directly labeling KH901, a tumor-specific oncolytic recombinant adenovirus, biodistribution of 125I-labeled compound in normal mice was investigated. 125I-KH901 was prepared by N-bromosuccinimide labeling method to find the optimal ratio of labeling response. The compounds were isolated and purified by Sephadex-G10 agarose and the radiochemical purity of compounds was analyzed by paper chromatography. The radioactivity biodistribution in mice was measured at different times after caudal vein injection with 0.1ml 125I-KH901. The labeling yield of 125I-KH901 was 78% and the radiochemical purity was 95% after purification by Sephadex-G10 agarose. Biodistribution revealed that the uptake of 125I-KH901 in liver was higher than in other organs at all time points of the experiment. 125I-KH901 was mainly concentrated in liver, kidneys, spleen and lung. It can be seen that N-bromosuccinimide labeling method is an optimal method with simple steps and high labeling yield in labeling KH901 with 125I. 125I-KH901 has a biodistribution trait which is an advantage to treating liver tumors.

[The diagnostic value of 99mTc-MIBI myocardial perfusion imaging for coronary artery disease: a systematic review].

This review aims to evaluate the quality of studies assessing the value of 99mTc-MIBI myocardial perfusion imaging in the diagnosis of coronary artery disease. OVID (1956 to 2006), CBMdisc (1978 to 2006), CNKI (2005 to 2006) and VIP (2005 to 2006) for relevant studies in English and Chinese were searched and identified. Quality assessment of diagnostic accuracy studies (QUADAS) items were used. Studies were classified and Meta-disc software was used to analyze sensitivity, specificity, positive likelihood ratio and negative likelihood ratio for the pooled analysis and heterogeneity test, then Asymmetric SROC curves were drawn for those without heterogeneity. In 29 articles included, the results of the pooled analysis showed that, as for rest, exercise and drug myocardial perfusion imaging, the pooled LR + were 2.209, 4.334 and 5.508, the pooled LR- were 0.224, 0.141 and 0.195, and for dipyridamole myocardial perfusion imaging, the pooled LR+ and LR- were 5.031 and 0.193, respectively. Besides, for stress myocardial perfusion imaging among the patients without myocardial infarction history, the pooled LR+ and LR- were 6.176 and 0.199, respectively. The biases from the 29 studies were mainly due to diagnostic test results review bias; variations were probable and were correlated with the spectrum of disease and inclusion criteria; the quality of report was moderate. The conclusion is that 99mTc-MIBI stress MPI, especially dipyridamole MPI, is valuable for diagnosing coronary artery disease.

Feasibility of herpes simplex virus type 1 mutants labeled with radionuclides for tumor treatment.

For over one hundred years, viruses have been recognized as capable of killing tumor cells. At present, people are still researching and constructing more suitable oncolytic viruses for treating different malignant tumors. Although extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is the most potential oncolytic virus, therapies based on herpes simplex virus type 1 vectors still arouse bio-safety and risk management issues. Researchers have therefore introduced the new idea of treating cancer with HSV-1 mutants labeled with radionuclides, combining radionuclide and oncolytic virus therapies. This overview briefly summarizes the status and mechanisms by which oncolytic viruses kill tumor cells, discusses the application of HSV-1 and HSV-1 derived vectors for tumor therapy, and demonstrates the feasibility and prospect of HSV-1 mutants labeled with radionuclides for treating tumors.

[Progess on research of herpes simplex virus type 1 mutants for cancer therapy].

For a long time past viruses have been recognized as being tumoricidal. At present, researchers are still pursuing studies and constructing more suitable oncolytic viruses for treating different malignant tumors. Herpes simplex virus type 1 (HSV-1) has been known as the most potential oncolytic virus among all the viruses. In this overview, we summarize the current situation of oncolytic viruses, the biology of HSV-1, its construction and application of its recombinant, and we debate on the feasibility and prospect of HSV-1 mutants labeled with radionuclides for cancer therapy.