"Percutaneous Transluminal Coronary Angioplasty (PTCA) remains limited by restenosis that occurs in 30 to 50% of patients with coronary artery disease. During the last decade, numerous agents have been used to prevent restenosis. Despite positive results in animal models, no pharmacological therapy has been found to significantly decrease the risk of restenosis in humans. These discrepancies between animal models and clinical situation were probably related to an incomplete understanding of the mechanism of restenosis. Neointimal thickening occurs in response to experimental arterial injury with a balloon catheter. Neointimal formation involves different steps: smooth muscle cell activation, proliferation and migration, and the production of extracellular matrix. The factors that control neointimal hyperplasia include growth factors, humoral factors and mechanical factors. Arterial remodeling also plays a major role in the restenosis process. Studies performed in animal and human subjects have established the potentials for "constrictive remodeling" to reduce the post-angioplasty vessel area, thereby indirectly narrowing the vessel lumen and thus contributing to restenosis. The reduction of restenosis rate in patients with intracoronary stent implantation has been attributed to the preventive effect of stent itself for this negative remodeling. In addition to these mechanisms for restenosis, intraluminal or intra-plaque thrombus formation, reendothelialization and apoptosis theories have been introduced and confirmed at least in part.
Angioplasty ; Animals ; Apoptosis ; Catheters ; Coronary Artery Disease ; Coronary Disease ; Coronary Restenosis ; Extracellular Matrix ; Humans ; Hyperplasia ; Intercellular Signaling Peptides and Proteins ; Models, Animal ; Myocytes, Smooth Muscle ; Stents ; Thrombosis

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

Radiation synovetomy with various radiopharmaceuticals has been used to alleviate pain and swelling of rheumatoid arthritis and related joint diseases for more than 40 years. It is an attractive alternative to the surgical synovectomy for the management of the various joint diseases. Recently, the development of new radiopharmaceuticals labeled with 90Y, 32P, 186Re, 188Re, 153Sm, 165DY and 166Ho, for the effective management of synovial inflammation and related arthritic problems are gaining attention. In this article the general concepts and the clinical application of radiation synovectomy are reviewed.
Arthritis ; Arthritis, Rheumatoid ; Inflammation ; Joint Diseases ; Joints* ; Radiopharmaceuticals

There is considerable interest in 188Re due to its favorable properties as a therapeutic radionuclide. 188Re and 99mTc act as a matched pair because of their similar chemical properties, and therefore methods of labeling with 99mTc can be applied to the labeling with 188Re. With appropriately chosen agents as carriers of 188Re, the labeling can be readily carried out using 188ReO4- in the presence of a reducing agent. 188Re radio pharmaceuticals based on 99mTc complexes have been synthesized and are currently being studied for clinical use. Some of them are shown to be suitable for therapeutic use and promising for radiotherapy in nuclear medicine.
Nuclear Medicine ; Radiopharmaceuticals ; Radiotherapy

188Re (beta=22 MeV; gamma=155 keV; T1/2=16.9 hours) is an attractive therapeutic radioisotope which is produced from decay of reactor-produced tungsten-188 parent (T1/2=69 days). 188W has been produced from the double neutron capture reaction of 186W. 188Re can be easily obtained by elution of saline on alumina based 186W/188Re generator, which is commercially available. Complexes labelled with 188Re have been developed for the radiotherapy treatment of diseases because of the desirable nuclear properties of the radioisotope and it's chemical properties similar to those of technetium, a well established diagnostic agent.
Aluminum Oxide ; Humans ; Neutrons ; Parents ; Radiotherapy ; Technetium

Although cerebrospinal fluid leakage is suggested as one of the causes of spontaneous intracranial hypotension, on]y a few cases with direct evidence of cerebrospinal fluid leakage on radionuclide cisternography have been reported in the literature Indirect evidences of cerebrospinal fluid leakage such as early visualization of the soft tissue and bladder or delayed migration of radiotracer have been observed in most patients with spontaneous intracranial hypotension. We report a case of spontaneous intracranial hypotension in which cerebrospinal fluid leakage was directly demonstrated by early dynamic imaging of spine on radionuclide cisternography. We suggest that early dynamic imaging of spine is an important adjunctive procedure in detecting cerebrospinal fluid leakage in patients with spontaneous intracranial hypotension.
Cerebrospinal Fluid* ; Humans ; Intracranial Hypotension* ; Spine ; Urinary Bladder

We report four cases of spontaneous intracranial hypotension that were investigated by radionuclide cisternography Tc-99m-diethylenetriamine pentaacetic acid radionuclide cisternography of all our patients showed direct sign of cerebrospinal fluid leakage as well as indirect signs of less activity than expected over the cerebral convexities and rapid appearance of bladder activity. The headache of all patients was eventually controlled with bed rest and hydration.
Bed Rest ; Cerebrospinal Fluid ; Headache ; Humans ; Intracranial Hypotension* ; Urinary Bladder

PURPOSE: The purpose of this study was to ascertain whether radiation adaptive response could be induced by Tc-99m-methylene diphosphonate (Tc-99m-MDP) in peripheral lymphocytes of patients undergoing bone scintigraphy. MATERIALS AND METHODS: Lymphocytes from 22 patients (6 males, 16 females, mean age 50+/-14 years) were collected before and after bone scintigraphy using 740 MBq Tc-99m-MDP. Lymphocytes from 10 controls (6 males, 4 females, mean age 43+/-7 years) were also collected. They were exposed challenge dose of 2 Gy gamma rays using a cell irradiator Number of ring-form and dicentric chromosomal per 600 cells (chromosomal aberrations) was counted under the light microscope. RESULTS: Chromosomal aberrations in patients before bone scintigraphy (385.1+/-30.5) was not different from that of controls (367.8+/-36.6). However, chromosomal aberrations in patients after bone scintigraphy was significantly decreased 192.6+/-22.1 (p=0.0001). CONCLUSION: Low dose gamma-irradiation by Tc-99m-MDP used for bone scintigraphy induces a cytogenetic adaptive response in peripheral lymphocytes.
Chromosome Aberrations ; Cytogenetics ; Female ; Gamma Rays ; Humans ; Lymphocytes* ; Male ; Radionuclide Imaging* ; Technetium Tc 99m Medronate

PURPOSE: Liquid beta emitter filled in angioplasty balloon could be used to perform endovascular balloon brachytherapy to prevent coronary artery restenosis. We investigated the dosimetry for Re-188-DTPA liquid-filled balloon and medical internal radiation dosimetry in case of balloon leakage. MATERIALS AND METHODS: We estimated radiation dose from an angioplasty balloon (20 mm lengfh, 3 mm diameter cylinder) to the adjacent vessel wall using Monte Carlo EGS4 code. We obtained time-activity curves of kidneys in normal dog and calculated Tmax, T1/2. Using MIRDOSE3 program, we estimated absorbed doses to the major organs (kidneys, bladder) and the whole body when we assumed that balloon leaked all the isotope contained. RESULTS: The radiation dose was 17.5 Gy at the balloon surface when we applied 3,700 MBq/ml of Re-188 for 100 seconds. Fifty percent of the energy deposited within 1 mm from the balloon surface. The estimated internal dose to the whole body was 0.005 mGy/MBq and 18.5 mGy for the spillage of 3,700 MBq of Re-188. CONCLUSION: We suggest that Re-188-DTPA can be used for endovascular balloon brachytherapy to inhibit coronary artery restenosis after angioplasty with tolerable whole body radiation dose in case of balloon rupture.
Angioplasty* ; Animals ; Brachytherapy* ; Coronary Vessels ; Dogs ; Kidney ; Radiometry ; Rupture ; Whole-Body Irradiation

PURPOSE: To determine whether Tc-99mMIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively Tc-99mMIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular Tc-99m-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr1 gene) overexpression. MATERIALS AND METHODS: We measured percentage uptake of Tc-99m-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of Tc-99m-MIBI were also evaluated with or without overexpression of mdr1 gene in cultured murine leukemia L1210 cells. RESULTS: The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of Tc-99m-MIBI was higher in mdr1 negative L1210 cells than those of mdr1 positive cells, and higher when incubated in 37 degree C than 4 degree C. In the presence of verapamil, cyclosporin or dipyridamole, Tc-99m-MIBI uptake was increased upto 604% in mdr1 positive cells. CONCLUSION: Cellular uptake of Tc-99m-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MDR-reversing agents increase cellular uptake. These results suggest that Tc-99m-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents In vitro.
Animals ; Cell Line ; Cyclosporine ; Dipyridamole ; Doxorubicin ; Drug Resistance, Multiple* ; Leukemia L1210 ; Leukemia* ; P-Glycoprotein ; Technetium Tc 99m Sestamibi* ; Verapamil ; Vincristine