For the distant metastasis of differentiated thyroid cancers, such as papillary thyroid carcinoma, follicular thyroid carcinoma, and Hurthle cell carcinoma, radioiodine therapy is one of the standard treatment methods after total thyroidectomy. Radioiodine is accumulated in thyroid cells and thyroid cancer cells through sodium iodide symporter which is located in the membrane of cells. This molecular target specific therapy renders a better prognosis and less adverse effects. Radioiodine 131I emits gamma ray for imaging and beta ray for treatment at the same time, we can monitor patients' specific distribution of radioiodine, which let us know unexpected metastasis lesions or differentiated status of thyroid cancer cells. In this article, I reviewed practical points of view about radioiodine therapy for distant metastasis of thyroid cancers such as methods for administration of radioiodine, patients' preparation before radioiodine treatment, follow up of patients, adverse effects, and radiation safety issues.
Adenocarcinoma, Follicular ; Beta Particles ; Carcinoma ; Enzyme Multiplied Immunoassay Technique ; Follow-Up Studies ; Gamma Rays ; Humans ; Ion Transport ; Linear Energy Transfer ; Membranes ; Neoplasm Metastasis ; Organothiophosphorus Compounds ; Prognosis ; Sodium Iodide ; Symporters ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy

AIMTo investigate the transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of beta-radiation.

METHODSTGF-beta1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with 90Sr/90Y.

RESULTSThe TGF-beta1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % +/- 10.5 % and 29.7 % +/- 4.6 %, respectively, while it was 64.8 % +/- 9.3 % and 28.6 % +/- 4.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-beta1 expression in the epithelia and stroma of BPH treated with 90Sr/90Y increased significantly (P <0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % +/- 3.7 % and 42.5 % +/- 6.8 %, respectively, and was 46.3 % +/- 8.2 % and 73.2 % +/- 12.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGF in the epithelia and stroma of BPH treated with a 90Sr/90Y prostatic hyperplasia applicator decreased significantly (P <0.01).

CONCLUSIONExposure of beta-rays had noticeable effects on BPH tissues, enhancing TGF-beta1 expression and inhibiting bFGF expression.

Aged ; Aged, 80 and over ; Beta Particles ; Case-Control Studies ; Fibroblast Growth Factor 2 ; metabolism ; radiation effects ; Gene Expression ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prostate ; metabolism ; radiation effects ; Prostatic Hyperplasia ; metabolism ; radiotherapy ; Strontium Radioisotopes ; therapeutic use ; Transforming Growth Factor beta ; metabolism ; radiation effects ; Transforming Growth Factor beta1 ; Yttrium Radioisotopes ; therapeutic use

BACKGROUND AND OBJECTIVES: Intracoronary radiation therapy for in-stent restenosis has been demonstrated to reduce restenosis and major adverse cardiac events. However, the long-term angiographic and clinical outcomes after beta radiation therapy have not been sufficiently evaluated. SUBJECTS AND METHODS: The long-term angiographic and clinical outcomes of 50 consecutive patients who had received beta-radiation therapy with an 188Re-MAG3-filled balloon after rotational atherectomy for diffuse in-stent restenosis (lesion length>10 mm) in native coronary arteries were evaluated. The radiation dose was 15 Gy at a depth of 1.0 mm into the vessel wall. RESULTS: The mean lesion length was 25.6+/-12.7 mm. Radiation was delivered successfully to all patients, without any procedural or in-hospital complications. At the 6-month angiogram, the restenosis rate was 10% (5/50). There were no major adverse cardiac events (MACE), such as death, myocardial infarction or target lesion revascularization (TLR), by the 6-month follow-up. Long-term clinical data were obtained from all patients during 30.1+/-4.5 months of follow-up. No myocardial infarction and one noncardiac death occurred during follow-up. A two-year follow-up angiogram was performed in 26 (58%) of 45 patients that showed a patent radiation segment at the 6-month angiogram. Significant narrowing of the diameter stenosis greater than 50% occurred in 6 (23%) of 26 patients between 6- and 24-months after the beta-radiation. Late TLR was performed in 6 patients. The rate of 30-month death-free survival and MACE-free survival were 98.0+/-2.0 and 86.9+/-5.0%, respectively. CONCLUSION: Beta-radiation using an 188Re-MAG3-filled balloon after rotational atherectomy is associated with favorable long-term angiographic and clinical outcomes.
Atherectomy, Coronary* ; Beta Particles ; Brachytherapy ; Constriction, Pathologic ; Coronary Restenosis ; Coronary Vessels ; Follow-Up Studies ; Humans ; Myocardial Infarction

OBJECTIVETo evaluate the effect of beta irradiation on intimal proliferation and apoptosis in vein grafts.

METHODSAutogenous vein graft model was established in 80 rats by transplanting the internal branch of the jugular vein to the carotid artery by end to end anastomosis. The veins were irradiated by (32)P solution before anastomosis. Two dose schedules were studied: control group (graft, nonirradiated) and radiation group (20 Gy). The grafted veins were harvested at 3, 1, 2 and 4 week respectively after the operation. intimal hyperplasia (IH), smooth muscle cell (SMC), proliferation, p53, bcl-2 and bax were observed pathologically and immunohistochemically. They were analyzed by a computerized system. The presence of apoptotic VSMC was demonstrated by TUNEL method.

RESULTThere was a significant decrease in the average intimal thickness at 7, 14 and 28 days (t = 15.694, P < 0.05) in the radiation group. Immunohistochemical analysis of PCNA indicated decreased positive cells in the radiation group compared with the controls at 1 and 2 weeks (t = 60.157, P < 0.01). Apoptosis of VSMC was higher in the radiation group than in the control group at 2 weeks (t = 56.176, P < 0.01). There was no significant difference in expression of P(53) between the two groups, and there was a significant increase in bax/bcl-2 in the radiation group at 2 weeks (t = 9.783, P < 0.05).

CONCLUSIONThese preliminary results demonstrated that low dose of beta irradiation in the vein graft inhibits SMC proliferation and induces the apoptosis of VSMC in rats.

Animals ; Apoptosis ; Beta Particles ; Brachytherapy ; Disease Models, Animal ; Graft Occlusion, Vascular ; metabolism ; pathology ; In Situ Nick-End Labeling ; Male ; Muscle, Smooth, Vascular ; pathology ; radiation effects ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Tumor Suppressor Protein p53 ; metabolism ; Tunica Intima ; pathology ; radiation effects

PURPOSE: The purposes of this study were to evaluate the biodistribution and effect of Ho-166 radionuclide by intra-arterial injection of the Ho-166 chitosan complex in dogs and to assess the clinical efficacy and side effects of this complex in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In an experimental study, 20 mCi of Ho-166 chitosan complex was injected into the left hepatic artery of six adult dogs. The distribution of radioactivity in each organ was calculated using a gamma camera scan at regular intervals. A beta ray radioactivity count (cpm) of blood and urine was performed periodically, and hematologic and hepatic function were regularly assessed. At 4, 8 and 12 weeks after intra-arterial injection, bone marrow and liver were pathologically evaluated. Twenty-five patients with a single, nodular HCC mass 3 -9 cm in diameter were treated by intra-arterial injection of Ho-166 chitosan complex, and immediately after the procedure a gamma camera scan was obtained. A beta ray radioactivity count(cpm) of blood was performed periodically, hematologic and hepatic function were regularly evaluated, and CT scans and angiograms were obtained 3 months after the procedure. On the basis of the CT and angiographic findings, the treatment effects were classified as complete (CR), partial (PR) or non-response(NR). RESULTS: In the animal study, blood radioactivity peaked immediately after injection and then declined rapidly. Urinary excretion was 0.17%. The proportion of radioactivity in each organ per whole body was 25% in the left lobe of the liver, 7% in the right lobe, 3% in the lung, 1.4 -3% in the bladder, and 2% in bone. WBC and platelet counts declined maximally at 3 -4 weeks and recovered at 12 weeks. The cellularity of bone marrow was 25% at 4 weeks and 55% at 12 weeks, findings which correlated well with the observed hematologic changes. In the clinical study of 25 HCC patients, CR was achieved in 17 (68%) cases, PR in 5 (20%) and NR in 3 (12%). At gamma camera imaging immediately after treatment, tumor radioactivity was localized in 76% of cases. In six cases (24%) WBC and platelet counts decreased 50% or more compared with their pretreatment level. In 67 -75% of cases, SGOT and SGPT were, within 1 -3 days, 2 -3 times higher than their pre-treatment level, and recovered at post 4 weeks. CONCLUSION: Ho-166 chitosan complex administrated intra-arterially localized the target organ with minimal side effects, and we therefore suggest that it may be used in the treatment of nodular and hypervascular HCC. Further study of its dosimetry and possible hematologic side reactions is needed, however.
Adult ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Beta Particles ; Bone Marrow ; Carcinoma, Hepatocellular* ; Chitosan* ; Dogs ; Gamma Cameras ; Hepatic Artery ; Humans ; Injections, Intra-Arterial* ; Liver ; Lung ; Platelet Count ; Radioactivity ; Radionuclide Imaging ; Tomography, X-Ray Computed ; Urinary Bladder

Matrix metalloproteinases have long been viewed as ideal candidates for proteinases that enables tumor cells to permeated basement membrane defenses and invade surrounding tissue. There is growing evidence that the MMPs have an expanded role, as they are important for the creation and maintenance of a microenvironment that facilitates growth and angiogenesis of tumors at primary and metastatic sites. MT-MMPs are not secreted but instead remaining attached to cell surfaces. Although not all of the MT-MMPs are fully characterized, MT-MMPs have important role in localizing and activating secreted MMPs. The MMP genes are transcriptionally responsive to a wide variety of oncogene, growth factors, cytokine, and hormones. Currently, a number of MMP inhibitors are being developed and some have reached clinical trials as anti-metastatic or anti-cancer therapies. MT1-MMP is involved in the activation of proMMP-2. MT1-MMP is significant not only as a tumor marker but as a new target for chemotherapy against cancer. The purpose of this study was to evaluate the effects of protein kinase C inhibitor(genistein) on the proliferation of HT1080 and expression of MT1-MMP mRNA. Human fibrosarcoma cell line HT1080 was cultured and divided 2 groups. The experimental group was treated with 100 microM genistein and incubated 12h, 24h for [3H]-thymidine uptake assay and northern hybridization individually. And the control group was treated with same amount of PBS for the above procedures. [3H]-thymidine incorporation was measured with beta ray detector. And RT-PCR and northern blotting for MT1-MMP mRNA was performed. The results were as follows 1. [3H]-thymidine uptake was reduced in experimental group with statistical significance. 2. MT1-MMP mRNA expression was significantly reduced in experimental group. These results showed that protein kinase C inhibitor (genistein) inhibited proliferation of HT1080 and almost completely blocked transcription of MT1-MMP mRNA. So, it is possible to use the protein kinase inhibitor (genistein) as anti-metastatic and anti-proliferative agent.
Basement Membrane ; Beta Particles ; Blotting, Northern ; Cell Line ; Drug Therapy ; Fibrosarcoma ; Genistein* ; Humans ; Intercellular Signaling Peptides and Proteins ; Matrix Metalloproteinase 14 ; Matrix Metalloproteinase Inhibitors ; Matrix Metalloproteinases ; Membranes* ; Neoplasm Metastasis ; Oncogenes ; Peptide Hydrolases ; Protein Kinase C ; Protein Kinases ; RNA, Messenger*

Coronary restenosis is still regarded as Achilles' Hill of interventional cardiology despite relentless efforts of many investigators. Recent experimental and clinical studies have suggested that both gamma and beta radiation can be reduce restenosis after angioplasty. Currently, intracoronary brachytherapy for the prevention of restenosis has become a new evolving treatment modality in interventional cardiology. This report discusses a physical aspect of gamma and beta radiation, initial clinical results and delivery systems used in intracoronary brachytherapy. We shall take a brief overview of methods and their advantages in intracoronary brachytherapy. Future work should provide further insight for the best way of treating restenosis.
Angioplasty ; Beta Particles ; Brachytherapy ; Cardiology ; Coronary Restenosis ; Humans ; Research Personnel

Rheumatoid arthritis(RA) is a chronic inflammatory disease of joints with proliferation of synovial epithelial tissue. Therapeutic approach of the RA consists of pharmacological and surgical interventions. Synovectomy is indicated in patients with progressive inflammatory signs and symptoms intractable to medical treatment including local intracavitary steroid injection. Recently, local injection of radionuclides which emit high energy beta rays are labeled with chemical compounds such as 90Y, 165Dy-ferric hydroxide macroaggregate and have been introduced as an alternative therapeutic modality to surgical synovectomy. Holmium-166 is one of beta emitter and Ho-166-chitosan complex was developed for radiation synovectomy. Preclinical trial is on-going at our hospital using Ho-166-chitosan. The procedure and methods of preclinical trial are discussed.
Arthritis, Rheumatoid ; Beta Particles ; Humans ; Joints ; Radioisotopes

PURPOSE: Holmium-166(H0-166) is a potent beta-emitter with a short half-life(26.83 hours) and high betaenergy(1.85MeV), and its necrotic effect on breast carcinoma has been proved. In cases of hepatocellularcarcinoma, Ho-166 can therefore be used for internal radiation therapy. The purpose of this study is to evaluatethe therapeutic effect of Ho-166 on hepatocellular carcinomas and to estimate the required dosage, according totheir size. MATERIALS AND METHODS: Tumor cells of hepatocellular carcinomas(SK-HEP1) were subcutaneouslyheterotransplanted into 71 nude mice and 71 hepatocellular carcinomas less than 2cm in diameter were grown. Ho-166was directly injected into a tumor at a dosage of between 0.5mCi(18.5MBq) and 3.0mCi(11MBq). After initialinjection of Ho-166, tumor uptake and radioactivity were indicated by gamma camera scanning. Hepatocellularcarcinomas in a control group of 20 mice were injected with 0.025ml of normal saline(n=10) and chitosansolution(n=10). Pathologic examination was performed and the necrotic tumor area was measured with an imageanalyzer. RESULTS: All specimens of Ho-166-injected hepatocellular carcinomas showed coagulation necrosisconsistent with radiation effect, while the control group did not show necrosis. As the injected dosage of Ho-166was increased, the necrotic area extended proportionally and the dosage required for total necrosis was calculatedaccording to tumor size. Gamma scintigraphy showed that injected Ho-166 had accumulated within the tumor, withoutthe accumulation of radioactivity in other organs ; the required dosage could be predicted on the basis ofradioactivity count indicated by a gamma camera. CONCLUSION: High-energy beta radiation emitted by Ho-166 can besufficient to kill tumor tissue without associated radiation damage to neighboring organs; intratumoral injectionis thought to be a promising therapeutic approach and a new method for the treatment of hepatocellular carcinoma.
Animals ; Beta Particles ; Breast Neoplasms ; Carcinoma, Hepatocellular* ; Gamma Cameras ; Mice* ; Mice, Nude ; Necrosis ; Radiation Effects ; Radioactivity ; Radionuclide Imaging

Intraperitoneal adminstration of radioisotopes is suggested to treat the metastatic ovarian cancer in the pertioneal cavity. Administering beta-emitting radioisotopes into the pertioneal cavity allows the maximum energy delivery to the cancerous cells of the pertioneal wall surface while sparing the normal cells located in deep site of the peritoneal wall. In this study, dose estimates of the peritoneal wall are provided to be used for prescribing the amount of 166Ho-chitosan complex administered. The 166Ho-chitosan complex diffused in the peritoneal fluid may attach to the peritoneal wall surface. The attachment fraction of 166Ho-chitosan complex to the peritoneal wall surface is obtained by simulating the ascites with Fischer rats. Both volume source in the peritoneal fluid and the surface source over the peritoneal wall surface are counted for the contribution to the peritoneal wall dose. The Monte Carlo code EGS4 is used to simulate the energy transfer of the beta particles emitted from 166Ho. A plane geometrical model of semi-infinite volume describes the peritoneal cavity and peritoneal wall. A semi-infinite plane of 10 micrometer in thickness at every 1 mm of depth in the peritoneal wall is taken as the target in dose estimation. Greater han 98 percents of attachment fraction has been observed from the experiments with Fischer rats. Given 1.3 microcurie/cm2 and 2.4 microcurie/ml of uniform activity density, absorbed dose is 123 Gy, 8.59 Gy, 3.00 Gy, 1.03 Gy, and 327 Gy at 0 mm, 1 mm, 2 mm, 3 mm, and 4 mm in depth to the peritoneal wall, respectively.
Ascites ; Ascitic Fluid ; Beta Particles ; Energy Transfer ; Ovarian Neoplasms ; Peritoneal Cavity ; Radioisotopes ; Rats, Inbred F344