Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas.
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BACKGROUND: Intraoperative radiation therapy (IORT) is one of the methods used to deliver a large single dose to the tumor tissue while reducing the exposure of normal surrounding tissue. However, the usefulness of intraoperative electron therapy for malignant gliomas has not been established. METHODS: During the period from 1987 to 1997, 32 patients with malignant gliomas were treated with IORT. The histological diagnoses were anaplastic astrocytoma in 11 patients and glioblastoma in 21 patients. Therapy consisted of surgical resection and intraoperative electron therapy using a dose of 12--15 Gy (median, 15 Gy). The patients later underwent postoperative external radiation therapy (EXRT) with a median total dose of 60 Gy. Each of the 32 patients treated with IORT was randomly matched with patients who had been treated with postoperative EXRT alone (control). Patients were matched according to histological grade, age, extent of tumor removal, and tumor location. RESULTS: In the anaplastic astrocytoma group, the one-, two- and five-year survival rates were 81%, 51% and 15%, respectively in the IORT patients and 54%, 43% and 21%, respectively in the control patients. In the glioblastoma group, one-, two- and five-year survival rates were 63%, 26% and 0%, respectively in the IORT patients and 70%, 18% and 6%, respectively in the control patients. There was no significant difference between survival rates in the IORT patients and control patients in either the anaplastic astrocytoma group or glioblastoma group. CONCLUSIONS: IORT dose not improve survival of patients with malignant gliomas compared to that of patients who have received EXRT alone. (+info)
SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology investigations in small laboratory animals: binding studies with (11)C-raclopride.
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Our aim was to show the ability of a recently developed beta(+)-range-sensitive intracerebral probe (SIC) to measure, in vivo, the binding of radioligands in small animals. METHODS: The potential of the device for pharmacokinetic studies was evaluated by measurement of the dynamic striatal binding of (11)C-raclopride, a well-documented D(2) dopaminergic receptor ligand, in rat brain after intravenous injection of the labeled compound. The effects of preinjection of the unlabeled ligand (raclopride, 2 mg/kg intravenously) and of increasing the synaptic dopamine level (amphetamine treatment, 1 mg/kg intravenously) or of depleting synaptic dopamine (reserpine pretreatment, 5 mg/kg intraperitoneally) on in vivo (11)C-raclopride binding were monitored by SIC. RESULTS: The radioactivity curves measured as a function of time were reproducible and consistent with previous studies using PET imaging (ratio of striatum to cerebellum, 2.6 +/- 0.3 after 20 min). Further studies showed significant displacement of (11)C-raclopride by its stable analog. Finally, the device proved its capacity to accurately detect changes in (11)C-raclopride binding after a sudden (amphetamine) or a gradual (reserpine) modulation of endogenous dopamine levels. CONCLUSION: These results show that the new device can monitor binding of PET ligands in anesthetized rodents in vivo, with high temporal resolution. (+info)
Radionuclide-antibody conjugates for single-cell cytotoxicity.
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BACKGROUND: Radioimmunotherapy has primarily utilized high-energy beta-particles, which are intended to kill macroscopic tumor masses. Such conjugates do not kill single cells or micrometastases efficiently. For killing single cells, it may be preferable to use radiation with a much shorter path length, such as alpha-particles or Auger or conversion electrons. METHODS: This selective review focuses on the use of radiolabeled antibody (Ab) conjugates to achieve single-cell kill. The advantages and disadvantages of particular types of radionuclides, the significance of intracellular localization of the Ab, and the potential clinical application of this approach are discussed. Potentially useful radionuclides are listed. RESULTS: Auger and conversion electrons can kill cells effectively, with at least 6 logs of cell kill. Abs on the cell surface are only slightly less potent than Abs internalized into the cytoplasm, and this is consistent with theoretical considerations. alpha-Particles kill single cells very effectively, but the short half-lives of the available alpha-particle emitters are probably a disadvantage. High-energy beta-particles can also kill single cells if they bind in sufficient amounts, but their disadvantage appears to be greater nonspecific toxicity. CONCLUSIONS: Single-cell kill can be obtained with radionuclide-Ab conjugates. The selection of the optimal radionuclide may depend on the details of the clinical situation, such as the size and accessibility of the tumor burden, and the particular Ab to be used. Direct comparisons of various radionuclides are required in order to identify the optimal approach. However, for single-cell kill, as required for therapy of micrometastases, the use of Auger and conversion electron emitters appears to have substantial advantages. While current methods limit the applicability of this approach to Abs having a high level of binding, it may be applicable to lower-density antigens if higher specific activities or more potent radionuclides can be used. Tumor cure may require a mixture of radionuclides intended to kill both single cells and large tumor masses. (+info)
High-dose intravascular beta-radiation after de novo stent implantation induces coronary artery spasm.
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BACKGROUND: Intracoronary brachytherapy is effective in preventing restenosis after coronary interventions. However, in vitro and animal studies have shown that irradiation produces immediate and sustained endothelial dysfunction. This study assesses the clinical relevance of impaired vasomotoric function induced by brachytherapy. METHODS AND RESULTS: We analyzed the occurrence of postradiation coronary artery spasms in 1 animal study and 2 clinical trials investigating the effects of high-dose intracoronary beta-radiation after de novo coronary artery stenting. Irradiated segments (IRSs) proximal and distal to the stent were studied by quantitative coronary angiography after stenting, after radiation, and at the end of the procedure. There was an 67% overall incidence of coronary artery spasm in the IRSs immediately after beta-radiation compared with 9% after sham treatment (P<0.001). Whereas in most cases this phenomenon was only minor or moderate, in 12 cases, 4 (22%) animals and 8 (28%) patients, severe coronary spasm (>90% diameter stenosis) with significant ECG-changes or hemodynamic instability was observed. Relief of spasms was protracted (mean time until complete relief of spasm 423+/-122 seconds) and required repetitive intracoronary administration of nitroglycerin (mean dose: 1.2+/-0.6 mg). CONCLUSIONS: Vasoconstriction is a frequent reaction of coronary arteries after high-dose intracoronary beta-radiation, necessitating repetitive administration of vasodilators. (+info)
Radioimmunotherapy for acute leukemia.
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BACKGROUND: The use of monoclonal antibodies to deliver radioactive isotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native monoclonal antibodies. In this article, we summarize the role of radioimmunotherapy in the treatment of leukemia. METHODS: The authors reviewed the published clinical trials of radioimmunotherapy in acute leukemia. RESULTS: Radioimmunoconjugates that emit beta-particles, such as 131I-anti-CD33, 90Y-anti-CD33, 131I-anti-CD45, and 188Re-anti-CD66c, deliver significant doses of radiation to the bone marrow and may be particularly effective when used as part of a conditioning regimen for hematopoietic stem cell transplantation. Radioimmunoconjugates that emit short-ranged alpha-particles, such as 213Bi-anti-CD33, are better suited for the treatment of low-volume or residual disease. CONCLUSIONS: Radiolabeled antibodies can be administered safely to patients with advanced leukemias and have significant antileukemic activity. Radiolabeled antibodies can potentially intensify the antileukemic effects of conditioning regimens when used in conjunction with hematopoietic stem cell transplantation. Whether or not radiolabeled antibodies improve the outcome of patients with leukemia remains to be demonstrated by randomized studies. (+info)
Dosimetric measurements in isolated human coronary arteries: comparison of commercially available iridium(192) with strontium/yttrium(90) emitters.
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BACKGROUND: Intravascular brachytherapy is being applied more and more in patients with coronary artery disease for the prevention of restenosis subsequent to balloon angioplasty, in particular after stent implantation. Several radiation sources (beta- and gamma-emitters) are available in clinical routine. It was the purpose of this study to compare the radiation doses at the level of the adventitia in diseased and stented human coronary arteries for (192)Ir and (90)Sr/Y emitters in routine use. In contrast to previously published work, we performed dosimetry instead of calculating depth-dose distribution by use of the Monte Carlo system. METHODS AND RESULTS: Postmortem calcified human coronary artery segments were stented and placed in an organ bath. Commercially available gamma-emitters ((192)Ir; Cordis Checkmate) and beta-emitters ((90)Sr/Y; Novoste Beta-Cath) were used. Relative dose distributions along the adventitia were measured by a specially designed scintillation detector system. Whereas dose perturbations caused by stents and calcified plaque were negligible for the (192)Ir source, radiation from the beta source was significantly impaired (as much as 40%) at the level of the adventitia (3.0-mm vessel diameter). Dose perturbation was clearly dependent on the extent and severity of calcification, less affected by stent material. CONCLUSIONS: Dose perturbation caused by calcified plaque and metallic stents is significant for beta-sources. This dosimetric difference between beta- and gamma-emitters in diseased coronary arteries should be considered when calculating doses in intravascular brachytherapy. (+info)
Effects of low chronic doses of ionizing radiation on antioxidant enzymes and G6PDH activities in Stipa capillata (Poaceae).
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Stipa capillata (Poaceae) seeds were harvested from a control area (displaying a gamma dose rate of 0.23 micro Sv h(-1)) (C plants) and from two contaminated areas (5.4 and 25 micro Sv h(-1)) on the Semipalatinsk nuclear test site (SNTS) in Kazakhstan. The plants were grown for 124 d in a greenhouse under controlled conditions and exposed to three different treatments: (0) control; (E) external gamma irradiation delivered by a sealed 137Cs source with a dose rate of 66 micro Sv h(-1); (E+I) E treatment combined with internal beta irradiation due to contamination by 134Cs and 85Sr via root uptake from the soil. The root uptake led to a contamination of 100 Bq g(-1) for 85Sr and 5 Bq g(-1) for 134Cs (of plant dry weight) as measured at harvest. The activity of SOD, APX, GR, POD, CAT, G6PDH, and MDHAR enzymes was measured in leaves. Under (0) treatment, all enzymes showed similar activities, except POD, which had higher activity in plants originating from contaminated areas. Treatment (E) induced an enhancement of POD, CAT, GR, SOD, and G6PDH activities in plants originating from contaminated areas. Only control plants showed any stimulation of APX activity. Treatment (E+I) had no significant effect on APX, GR, CAT, and POD activities, but MDHAR activity was significantly reduced while SOD and G6PDH activities were significantly increased. The increase occurred in plants from all origins for SOD, with a greater magnitude as a function of their origin, and it occurred only in plants from the more contaminated populations for G6PDH. This suggests that exposure to a low dose rate of ionizing radiation for almost a half century in the original environment of Stipa has led to natural selection of the most adapted genotypes characterized by an efficient induction of anti-oxidant enzyme activities, especially SOD and G6PDH, involved in plant protection against reactive oxygen species. (+info)
Randomized trial of 90Sr/90Y beta-radiation versus placebo control for treatment of in-stent restenosis.
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BACKGROUND: After conventional treatment of in-stent restenosis, the incidence of recurrent clinical restenosis may approach 40%. We report the first multicenter, blinded, and randomized trial of intracoronary radiation with the use of a 90Sr/90Y beta-source for the treatment of in-stent restenosis. METHODS AND RESULTS: After successful catheter-based treatment of in-stent restenosis, 476 patients were randomly assigned to receive an intracoronary catheter containing either 90Sr/90Y (n=244) or placebo (n=232) sources. The prescribed dose 2 mm from the center of the source was 18.4 Gy for vessels between 2.70 and 3.35 mm in diameter and 23.0 Gy for vessels between 3.36 and 4.0 mm. The primary end point, ie, clinically driven target-vessel revascularization by 8 months, was observed in 56 (26.8%) of the patients assigned to placebo and 39 (17.0%) of the patients assigned to radiation (P=0.015). The incidence of the composite including death, myocardial infarction, and target-vessel revascularization was observed in 60 (28.7%) of the patients assigned to placebo and 44 (19.1%) of the patients assigned to radiation (P=0.024). Binary 8-month angiographic restenosis (> or =50% diameter stenosis) within the entire segment treated with radiation was reduced from 45.2% in the placebo-treated patients to 28.8% in the 90Sr/90Y-treated patients (P=0.001). Stent thromboses occurred in 1 patient assigned to placebo <24 hours after the procedure and in 1 patient assigned to 90Sr/90Y at day 244. CONCLUSIONS: The results of this study demonstrated that beta-radiation using 90Sr/90Y is both safe and effective for preventing recurrence in patients with in-stent restenosis. (+info)