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[Radiotherapy of intraocular tumors with Ruthenium-106-containing, beta-emitting ophthalmic applicators. Experiences with treatments performed between 1986 and 1999 in Hungary].

AIM: Till October 15, 2004, 312 patients were irradiated with Ruthenium-106-containing ophthalmic applicators at the Department of Ophthalmology, Medical Faculty, University of Debrecen. In this paper we report on experience gained with the irradiation of 187 patients, treated between 1986 and 1999, whose follow-up time interval was at least 5 years. PATIENTS AND METHODS: The distribution according to diagnosis of the patients irradiated between 1986 and 1999 were: choroidal melanoma 148, retinoblastoma 15, retinal angioma 9, carcinoma metastasis 4, subretinal neovascularization 11. The instruments purchased from the German Bebig firm were sutured under surgical circumstances onto the sclera, and were removed from the eye with another operation. The applied dose calculated to the inner surface of the tumors was 100 Gy in the case of choroidal melanomas, and 50 Gy in the case of retinoblastomas. RESULTS: From the patients irradiated because of malignant intraocular tumors 154 (95.7%) were evaluated. From the evaluated patients 148 (96.1%) are alive. Among the living patients 4 (2.7%) is suffering from distant metastasis. From the irradiated eyes 148 (96.1%) could be saved. Six eyes had to be enucleated, 1 eye because of phthisis bulbi, 2 because of hemorrhagic glaucoma, and 3 because of uncontrollable tumor growth. DISCUSSION: With the help of radioactive isotope-containing applicators the intraocular malignant tumors can be destroyed, so that the eyes can be saved with useful vision, without risking the patients' life.

Beta Particles↗

Bremsstrahlung radiation exposure from pure beta-ray emitters.

UNLABELLED: With increasing therapeutic use of radionuclides that emit relatively high-energy (>1 MeV) beta-rays and the production in vivo of bremsstrahlung sufficient for external imaging, the potential external radiation hazard warrants evaluation. METHODS: The exposure from a patient administered beta-ray-emitting radionuclides has been calculated by extending the National Council on Radiation Protection and Measurement model of a point source in air to account for biologic elimination of activity, the probability of bremsstrahlung production in vivo and its mean energy and the absorption by the patient's body of the bremsstrahlung thus produced. To facilitate such calculations, a quantity called the "specific bremsstrahlung constant" (in C/kg-cm2/MBq-h), betaBr, was devised and calculated for several radionuclides. The specific bremsstrahlung constant is the bremsstrahlung exposure rate (in C/kg/h) in air at 1 cm from a 1 MBq beta-ray emitter of a specified maximum beta-ray energy and frequency of emission in a medium of a specified effective atomic number. RESULTS: For pure beta-ray emitters, the retained activities at which patients can be released from medical confinement (i.e., below which the effective dose equivalent at 1 m will not exceed the maximum recommended value of 0.5 cSv for infrequently exposed members of the general public) are extremely large: on the order of hundreds of thousands to millions of megabecquerels. CONCLUSION: Radionuclide therapy with pure beta-ray emitters, even high-energy beta-ray emitters emitted in bone, does not require medical confinement of patients for radiation protection.

Beta Particles↗

Effects of prenatal low-dose beta radiation from tritiated water on learning and memory in rats and their possible mechanisms.

Pregnant adult Wistar rats were randomly divided into four groups. Three of these groups were irradiated with beta rays by a single intraperitoneal injection of tritiated water ((3)H(2)O) administered on the 13th day of gestation. The doses absorbed by their offspring were estimated to be 4.6, 9.2 and 27.3 cGy. The influence of radiation on the postnatal learning ability and memory behavior and on brain development of the offspring was investigated. The number of pyramidal cells (in areas CA1, CA2, CA3 and CA4) and neurons in the hippocampus of the offspring was also measured. In addition, the Ca(++) conductance of hippocampal pyramidal cells cultured in vitro was observed. The results showed that an exposure to 4.6 cGy could prolong avoidance response time significantly and decrease the number of hippocampal pyramidal cells in the CA1 area compared to controls. An exposure to 9.2 cGy significantly decreased the establishment of conditioned reflexes and the number of hippocampal pyramidal cells in the CA3 area. This exposure also induced the degeneration and malformation of hippocampal neurons cultured in vitro, in addition to decreasing the number of hippocampal neurons observed on each culture day. A dose of 27.3 cGy significantly decreased brain and body weights and the maximum electric conductance of Ca(++) in hippocampal pyramidal neurons. In general, dose-dependent effects were observed for most of the parameters assessed in the present study. Possible mechanisms are discussed.

Animals↗

A method for patient-specific absorbed dose estimation for internal beta emitters.

The purpose of the study was to determine a technique for estimating patient-specific absorbed radiation doses in radioimmunotherapy and other internal emitter therapies. Beta Radiation sources were considered, with 90Y being the radionuclide of primary interest. Organ uptake of activity was determined using a merged set of computed tomography and planar nuclear images. Estimation of local absorbed dose was accomplished using a voxel source kernel. Voxel size was 0.2 x 0.2 x 0.5 cm; dimensions were from the digital resolution of the nuclear and computed tomography data sets. Dose-volume histograms were also obtained due to the voxel nature of the estimations. Organ dose estimates were made for two patients receiving the chimeric anticarcinoembryonic antigen antibody cT84.66. Considerable variation was observed when comparing the voxel kernel results with medical internal radiation dosimetry values obtained via the MIRDOSE3 program. Primary uncertainty in the organ dose estimates was determined to be due to the variation in organ mass. By correcting the S values in that program by the organ mass ratio, we found generally good agreement between our method and MIRDOSE3. We conclude that patient-specific absorbed doses can be estimated for 90Y-labeled antibodies.

Beta Particles↗

Validation of an analytical expression for the absorbed dose from a spherical beta source geometry and its application to micrometastatic radionuclide therapy.

The purpose of this study was to validate an analytical expression for the absorbed-dose calculation from the spherical source of beta-emitting radionuclides and to apply it to micrometastases treated with radiolabeled monoclonal antibodies. The self-absorbed fractions from I-131 and P-32 uniform spherical sources were calculated using the analytical expression introduced by P. K. Leichner (J. Nucl. Med., 35: 1721-1729, 1994). The calculated absorbed fractions were compared with previously reported values and were found to be in reasonable agreement, with a maximum difference of 15% for smaller masses and a long-range beta emitter. The expression was subsequently applied to estimate the absorbed dose within spheroid models with nonuniform penetration of radiolabeled antibody. The corresponding absorbed dose for I-131 was compared with reported micro-thermoluminescence dosimeter measurements and found to be in good agreement. This work has independently substantiated the methodology outlined by Leichner and may be reliably incorporated into new software developments for radionuclide dosimetry treatment planning.

Beta Particles↗

[Cellular reactions induced by chronic exposure to 14C beta-rays].

In V-79 cells the Effects of chronic exposure on induction of chromosome aberrations and abnormal metaphases as well as on efficiency of subsequent exposure to 2 Gy gamma-rays were investigated. It was found that chronic exposure increased the yield of chromosome aberrations as well as abnormal metaphases (spread-metaphases and apoptotic metaphases). In spite of the level of damages in cells, the chronic beta-exposure protected cells against the additional induction of chromosomal aberrations by subsequent exposure to higher acute dose of gamma-irradiation. Cytogenetic adaptive response was retained in the surviving progeny of irradiated cells which were cultured in free medium during 40, 70 days or one year after chronic exposure. At this time the level of residual chromosome aberrations, colony forming ability and distribution of the cells by the number of chromosomes were almost the same as in unirradiated cells. However, the high level of abnormal metaphases and half as much of cells in colony in the surviving progeny of irradiated cells in comparison with unirradiated cell, allow us to suggest that the chronic exposure induced the selection of adaptive forms in condition of the higher level of radiation.

Adaptation, Biological↗

Rectal biopsy in type 4 glycogenosis. An ultrastructural cytochemical study.

Rectal biopsy material from a patient with type 4 glycogenosis was studied by ultrastructural cytochemical methods. The diagnosis of the disease was made on the basis of the patient's clinical history, the autopsy findings, and the histopathological features. Numerous large macrophages were observed in the rectal mucosa. They contained large vacuoles filled with filamentous material and small granules. This amylopectin was stained by the Thiery method (periodic acid-thiocarbohydrazide-silver proteinate) after 18 hours of exposure to thiocarbohydrazide; only 30 minutes was sufficient to demonstrate seemingly normal beta-glycogen particles in epithelial cells.

Autopsy↗

Late stent malapposition occurring after intracoronary beta-irradiation detected by intravascular ultrasound.

We report a case of late stent malapposition occurring 6 months after intracoronary beta-irradiation detected by three-dimensional intravascular ultrasound, in spite of good apposition immediately after the procedure. Volumetric quantification revealed that stent volume remained unchanged, whereas total vessel volume increased by 13% after 6 months within the stent area. The increase of the vessel volume took place mainly in the proximal part of the stent, where the malapposition was located.

Angioplasty, Balloon, Coronary↗

Physics of vascular brachytherapy.

Basic physics plays an important role in understanding the clinical utility of radioisotopes in brachytherapy. Vascular brachytherapy is a very unique application of localized radiation in that dose levels very close to the source are employed to treat tissues within the arterial wall. This article covers basic physics of radioactivity and differentiates between beta and gamma radiations. Physical parameters such as activity, half-life, exposure and absorbed dose have been explained. Finally, the dose distribution around a point source and a linear source is described. The principles of basic physics are likely to play an important role in shaping the emerging technology and its application in vascular brachytherapy.

Arteries↗

Compassionate use of intracoronary beta-irradiation for treatment of recurrent in-stent restenosis.

Recurrent in-stent restenosis after balloon angioplasty poses a serious management problem. Previously g-radiation has been shown to be effective in patients with in-stent restenosis. The aim of the study was to determine the feasibility and safety of b-radiation in patients with recurrent in-stent restenosis. From May 1997 to December 1998, 18 patients were treated with balloon angioplasty (n = 8) or laser (n = 10), followed by intracoronary b-radiation at a prescribed dose of 16 Gray at 2 mm from the source, for reference diameters by quantitative coronary angiography < 3.25 mm or 20 Gray for reference diameters > or =3.25 mm. Vessels treated were as follows: left anterior descending: (n = 5); circumflex: (n = 4); right coronary artery: (n = 6); saphenous vein graft: (n = 3). Average recurrence rate was 2.4 +/- 0.7 and the restenotic length was 16 +/- 7 mm. b-radiation was successfully delivered in all patients. Two patients presented complications related to laser debulking: a non-Q wave myocardial infarction in one and a re-angioplasty due to uncovered distal dissection in another. Geographical miss, defined as an area which has been injured but not covered by the radiation source, was demonstrated in 8 patients. Seventeen patients (94%) completed the 6-month angiographic follow-up. Restenosis (> 50% Diameter Stenosis) was observed in 9 patients (53%), leading to target lesion revascularization in 8 patients (47%). Six of the 9 restenoses were located in areas with geographical miss. Intracoronary b-radiation for recurrent in-stent restenosis appears to be a safe and feasible management strategy. However, the mismatch between injured and irradiated area may lead to failure of this therapy.

Aged↗

[Quantitative regularities for clinical manifestations of radiation injury in large-sized laboratory animals exposed to supralethal radiation doses Gamma-neutron and electron biological effectiveness as influenced by exposure conditions and dose distribution in the animal body].

The damaging effect of gamma-neutron radiation over a wide neutron-energy range, with average values of 0.37 and 1.2 MeV, and that of electrons with an average electron energy of 25 MeV have been compared in dogs and two monkey species exposed to a broad range of supralethal doses. An analysis of absorbed dose distribution in critical organs and systems has shown the highest effect of gamma-neutron radiation with an average neutron energy of 1.2 MeV. With severity of early clinical manifestations of damage as a criterion, electrons have appeared the most effective. The radiosensitivity of animals grew in the order as follows: dog-->M. fascicularis-->P. hamadryas.

Animals↗

[Can radiotherapy reduce the frequency of restenosis after coronary angioplasty?].

Today, percutaneous transluminal coronary angioplasty (PTCA) is the most important treatment modality for coronary artery disease. However, restenosis occurs in 20-40% of the vessels in spite of the use of stents. Intravascular radiation therapy has reduced the frequency of restenosis in both animal studies and clinical trials. Recent randomized trials have shown a reduction in the order of 30% after irradiation. A number of techniques which use different sources of radiation (beta vs. gamma radiation) are under investigation. This review gives and update of intravascular radiation therapy, including a discussion of ongoing trials. There is a great need, also in Norway, for treatment modalities that reduce the frequency of restenosis after PTCA. It would seem imperative that we start a discussion of whether and when intravascular radiation therapy should be available in Norway. Implementation requires planning on a national level with regard to investment in equipment and training.

Angioplasty, Balloon, Coronary↗

[Frequency of dominant lethal mutations induced by combined exposure to incorporated 137Cs and external gamma-irradiation in mice].

The genetic effect of combined exposure to incorporated 137Cs and external gamma-irradiation was studied in germ cells of male mice. The activity of incorporated 137Cs was 3.7 x 10(4) Bq/g. The dose of external gamma-irradiation was 1.5 Gy. In the case of combined exposure, mice were treated with a cesium solution immediately after irradiation. The genetic effect was estimated by the frequency of dominant lethal mutations (DLM) induced at different stages of spermatogenesis. Upon combined exposure to external and internal irradiation, the frequency of DLM in premeiotic cells significantly exceeded the total frequency of DLM induced by separate exposure to external and internal irradiation; i.e., a marked synergistic interaction of external and internal irradiation was observed.

Animals↗