RESUMEN
Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting ß(-) particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The (188)W/(188)Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) (188)Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent (188)W radionuclide have been a major impediment in the progress of application of (188)Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade (188)W/(188)Re generators. Since the specific activity of (188)W used in the generator is relatively low 185 GBq( < 5 Ci)/g], the eluted (188)ReO(4)(-) can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful (188)ReO(4)(-) solutions. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on (188)Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability and use of (188)Re including a discussion of why broader use of (188)Re has not progressed as expected as a popular radionuclide for therapy.
Asunto(s)
Neoplasias/radioterapia , Radioisótopos/aislamiento & purificación , Generadores de Radionúclidos , Radiofármacos/síntesis química , Renio/aislamiento & purificación , Adsorción , Anticuerpos Monoclonales/uso terapéutico , Artritis Reumatoide/radioterapia , Neoplasias Óseas/radioterapia , Carcinoma Hepatocelular/radioterapia , Cromatografía/métodos , Enfermedad Coronaria/radioterapia , Combinación de Medicamentos , Diseño de Equipo , Humanos , Aceite Yodado/uso terapéutico , Neoplasias Hepáticas/radioterapia , Dolor Musculoesquelético/prevención & control , Compuestos Organometálicos/uso terapéutico , Cuidados Paliativos/métodos , Péptidos/uso terapéutico , Radioinmunoterapia/métodos , Radioisótopos/química , Radioisótopos/uso terapéutico , Radiofármacos/química , Radiofármacos/uso terapéutico , Renio/química , Renio/uso terapéutico , Neoplasias Cutáneas/radioterapia , Succímero/uso terapéuticoRESUMEN
PURPOSE: The use of 192Ir brachytherapy for the treatment of in-stent restenosis of the coronary arteries has shown promising clinical results. This paper investigates the radiation exposure of catheterization laboratory staff associated with the performance of this procedure. METHODS AND MATERIALS: Cath lab staff were monitored using personal monitors (shielded against fluoroscopic x-rays) during the performance of eleven cases using nominal 10 GBq 192Ir sources. Staff positions in the lab were simultaneously tracked by video cameras. Direct measurements were also made using a survey meter. Treatments were administered in a conventional cardiac-catheterization-laboratory. RESULTS: The dosimeter readings were analyzed in combination with the radiation survey and time motion survey. Brachytherapy procedural times for the cardiologist, oncologist, physicist, and angiographic assistants were, respectively, 26 +/- 24, 401 +/- 132, 486 +/- 148, and 7 +/- 13 s per case (mean +/- standard deviation). Readings of the personnel monitors were low. Credible upper limits of the respective doses are estimated to be less than 10, 10, 7, and 5 microSv per procedure. Auxiliary shields reduced the dose to individuals located outside of the catheterization laboratory to less than 0.5 microSv per procedure. CONCLUSIONS: The average radiation dose received by laboratory personnel during a representative 192Ir endocoronary brachytherapy procedure is estimated to be less than 0.1% of the NCRP recommended annual radiation worker's Maximum Permissible Dose (1% of the general public's MPD). This level is justifiable as long as the use of 192Ir benefits patients by producing an improved clinical outcome relative to the use of a less penetrating radionuclide or the application of alternative therapies. Further optimization of the delivery procedure is expected to reduce staff dose.
Asunto(s)
Braquiterapia/normas , Monitoreo del Ambiente/métodos , Dosimetría por Película , Rayos gamma , Oclusión de Injerto Vascular/radioterapia , Personal de Salud , Exposición Profesional/análisis , Braquiterapia/efectos adversos , Braquiterapia/métodos , Enfermedad Coronaria/radioterapia , Humanos , Radioisótopos de Iridio/análisis , Exposición Profesional/prevención & control , Exposición Profesional/normas , Dosis de Radiación , Valores de Referencia , Grabación en VideoRESUMEN
BACKGROUND: The major limitation of coronary stenting is restenosis due to exaggerated neointimal thickening. We evaluated a positron-emitting V48 nitinol stent in a porcine coronary model of restenosis. METHODS AND RESULTS: Pigs (n = 16) received a control nonradioactive and a V48 stent (1.5 or 10.6 muCi) randomized to the left anterior descending artery (LAD) and right coronary artery (RCA). Histology, morphometric variables, and strut injury scores were evaluated after 32 days. Peristrut fibrinoid deposits were greater in the high-dose group (p < 0.0001). Control stent area stenosis (AS) and mean neointimal thickness (NIT) correlated with injury (r = 0.81 and 0.79, respectively). Higher-dose stents reduced AS by 20% (0.57 +/- 0.13 vs. 0.71 +/- 0.16; p = 0.029) and mean NIT by 35% (0.44 +/- 0.16 vs. 0.71 +/- 0.24mm; p = 0.001) compared with controls. Lower-dose 1.5-muCi stents did not differ from controls. NIT over individual struts was reduced in the high-dose group compared with controls by 0.18 mm for grade 1 injury, 0.31 mm for grade 2, and 0.38 mm for grade 3 (p < 0.02 for all comparisons). CONCLUSIONS: 1.5-muCi V48 nitinol stents did not influence vessel histology or restenotic parameters in pig coronary arteries. In contrast, 10.6-muCi stents created a distinctive histological picture consisting of increased fibrinoid deposits on the neointimal-facing side of the struts without cellular organization. Higher dose radioactive stents significantly reduced AS and mean NIT. The reduction in neointimal thickening was greatest when the depth of strut penetration into the vascular wall was most severe.
Asunto(s)
Enfermedad Coronaria/radioterapia , Radioisótopos/uso terapéutico , Vanadio/uso terapéutico , Aleaciones , Animales , Enfermedad Coronaria/patología , Enfermedad Coronaria/prevención & control , Vasos Coronarios/lesiones , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Femenino , Masculino , Recurrencia , Stents , PorcinosRESUMEN
PURPOSE: Recurrence of obstructive coronary arterial lesions (restenosis) after angioplasty remains a significant clinical problem. Ionizing radiation, at doses >10 Gy administered locally to the angioplasty site, has been shown to inhibit restenosis in porcine coronary arteries, but lower doses are ineffective. Methods that will allow delivery of lower doses of radiation while retaining the antirestenotic efficacy observed at the higher doses are desirable. Hypoxic cells are known to be radioresistant; accordingly, we hypothesized that increasing blood oxygenation through the use of the TherOx Aqueous Oxygen system would lower the doses of endovascular radiation required for the prevention of restenosis. MATERIALS AND METHODS: Five swine were studied as follows: balloon injury + oxygen alone was performed in two swine. Each swine had a balloon overstretch injury in two arteries, left anterior descending (LAD) and either right coronary artery (RCA) or left circumflex (LCX) artery (three arteries total). Balloon injury + oxygen followed by intracoronary irradiation was performed in a further three swine (six arteries). Controls consisted of arteries treated with 0, 5, or 15 Gy of 192Ir alone. RESULTS: Arteries treated with the TherOx Aqueous Oxygen system alone were indistinguishable from arteries treated without oxygenation except for a larger adventitial area (5.29 +/- 0.20 vs. 2.77 +/- 0.28 mm2; p < 0.05). Arteries treated with the TherOx Aqueous Oxygen system along with 5 Gy of 192Ir exhibited a greater injury-corrected intimal area than arteries treated with radiation alone (0.76 +/- 0.18 vs. 0.33 +/- 0.08 mm2; p < 0.05). Neither thrombosis rate nor thrombus area was significantly different in arteries receiving the TherOx Aqueous Oxygen as compared with controls. CONCLUSIONS: The TherOx Aqueous Oxygen system is safe in the context of balloon overstretch injury, but decreases the antirestenotic efficacy of 5 Gy of 192Ir. These findings suggest that hypoxia does not seem to be a major contributor to the dose of radiation required for suppression of neointima, at least when using noncentered gamma radiation delivery systems.
Asunto(s)
Braquiterapia , Enfermedad Coronaria/radioterapia , Oxigenoterapia Hiperbárica , Animales , Enfermedad Coronaria/patología , Enfermedad Coronaria/prevención & control , Vasos Coronarios/patología , Radioisótopos de Iridio/uso terapéutico , Dosificación Radioterapéutica , Recurrencia , PorcinosRESUMEN
PURPOSE: Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplasty reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments. METHODS AND MATERIALS: Analytical calculations of dose distributions and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied. RESULTS: Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15-20 Gy are required to a length of 2-3 cm of vessel wall (2-4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored. CONCLUSIONS: Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal. A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.
Asunto(s)
Braquiterapia , Enfermedad Coronaria/radioterapia , Modelos Cardiovasculares , Radioisótopos/administración & dosificación , Dosificación Radioterapéutica , Enfermedad Coronaria/terapia , Humanos , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Iridio/administración & dosificación , Paladio/administración & dosificación , Radioisótopos de Fósforo/administración & dosificación , Recurrencia , Radioisótopos de Estroncio/administración & dosificaciónRESUMEN
The article sums up numerous investigations of the authors on studying different parameters of membrane-dependent properties of erythrocytes and thrombocytes after UV irradiation of blood samples, mixing of irradiated and nonirradiated blood, transfusions of UV-irradiated auto blood. It was shown that membranotropic action of UV-irradiated blood and transfusion of UV-irradiated blood are responsible for rheological and hemostatic properties of blood.