phosphorus-radioisotopes and Constriction--Pathologic

For LDR-brachytherapy, a limited number of implant geometries and materials are available. To avoid wound healing related hyper-proliferation (stenosis, keloids) a novel radioactive foil system was developed based on beta emitting (32)P, which can be easily integrated in existing implants such as urethral catheters or bile duct stents. As substrate material for these foils PEEK (polyetherethercetone) was chosen because of its radiation hardness during neutron activation of (32)P. The activity was determined by liquid scintillation counting and gamma spectroscopy, dose distributions were measured with scintillation detectors and radiochromic films. The correlation between activity and dose was checked by Monte-Carlo-simulations (Geant4). Prototypes of the (32)P-implants have shown in wash-out tests the required tightness for sealed radioactive sources. In animal tests on urethra and bile duct, the uncomplicated and save application of (32)P-foils mounted on standard implants has been demonstrated, which is almost unchanged due to the simple radiation protection with plexiglass. This concept of radioactive implants with integrated (32)P-foils could extend essentially the application possibilities of LDR-brachytherapy.

Topics: Brachytherapy; Constriction, Pathologic; Equipment Design; Equipment Failure Analysis; Gastroenterology; Humans; Phosphorus Radioisotopes; Prostheses and Implants; Radiopharmaceuticals; Urology

Radiolabeled drug-eluting stents have been proposed recently as a novel method to potentially reduce restenosis in coronary arteries. A P-32 labeled oligonucleotide (ODN) loaded on a polymer coated stent is slowly released in the arterial wall to deliver a therapeutic dose to the target tissue. However, the relatively low proportion of drugs transferred to the arterial wall (<2%-5% typically) raises questions about the degree to which radiolabeled drugs eluted from the stent can contribute to the total radiation dose delivered to tissues. A three-dimensional diffusion-convection transport model is used to model the transport of a hydrophilic drug released from the surface of a stent to the arterial media. Large drug concentration gradients are observed near the stent struts giving rise to a nonuniform radiation activity distribution for the drug in the tissues as a function of time. A voxel-based kernel convolution method is used to calculate the radiation dose rate resulting from this activity build-up in the arterial wall based on the medical internal radiation dose formalism. Measured residence time for the P-32 ODN in the arterial wall and at the stent surface obtained from animal studies are used to normalize the results in terms of absolute dose to tissue. The results indicate that radiation due to drug eluted from the stent contributes only a small fraction of the total radiation delivered to the arterial wall, the main contribution coming from the activity that remains embedded in the stent coating. For hydrophilic compounds with rapid transit times in arterial tissue and minimal binding interactions, the activity build-up in the arterial wall contributes only a small fraction to the total dose delivered by the P-32 ODN stent. For these compounds, it is concluded that radiolabeled drug-eluting stent will not likely improve the performance of radioactive stents for the treatment of restenosis. Also, variability in the delivery efficacy of drug delivery devices makes accurate dosimetry difficult and the drug washout in the systemic circulatory system may yield an unnecessary activity build-up and dose to healthy organs.

Topics: Arteries; Constriction, Pathologic; Coronary Restenosis; Coronary Vessels; Diffusion; Heparin; Humans; Models, Statistical; Oligonucleotides; Phosphorus Radioisotopes; Polymers; Radiometry; Stents; Time Factors

3D dose distributions are calculated for a 32P impregnated stent and a 198Au stent for intravascular brachytherapy with the EGS4 Monte Carlo simulation code. The stents were modeled as a combination of eight helicoidal struts. This allowed investigation of the effect of the stent geometry and the electron absorption in the strut material on the dose distributions. Absorbed dose to water was calculated at radial distances ranging from 50 microm to 5 mm from the stent surface. The dose distributions around the stents are compared to the dose distribution around an intravascular brachy-therapy 192Ir source, also calculated with the EGS4 Monte Carlo code. The dose profiles near the struts show hot spots. At 50 microm distance a peak to valley ratio of 3 for 32P and 6 for 198Au in the dose distribution is obtained. For both the isotopes the inhomogeneities decrease with distance and at a radial depth of 350 microm the effect becomes negligible. The calculations showed the importance of the effect of the absorption in the stent material as this leads to a dose decrease to 67% for the 198Au stent and to 77% for 32P near the stent at a distance of 2 mm from the stent axis. It is concluded that from the dosimetric point of view, the 198Au stent is inferior to the 32P stent and the 192Ir source. Application of the 198Au stent in clinical practice requires further investigation of the importance of the adventitia in the restenosis process, and the tolerance dose of the intima.

Topics: Angioplasty, Balloon, Coronary; Biophysical Phenomena; Biophysics; Blood Vessels; Brachytherapy; Constriction, Pathologic; Gold Radioisotopes; Humans; Microscopy, Electron, Scanning; Monte Carlo Method; Phosphorus Radioisotopes; Radiotherapy Planning, Computer-Assisted; Stents

The objective of this paper was to provide an update on the clinical and experimental evaluation of radioactive stents for the prevention of restenosis.. Direct ion implantation of 32P onto the surface of a 15-mm length balloon expandable stainless-steel Palmaz-Schatz stent was employed to render this commercially available vascular stent radioactive. 32Phosphorous, a pure beta-particle-emitting radioisotope, was selected because of its short half-life (14.3 days) and limited range of tissue penetration (3-4 mm). The vascular response to radioactive 7-mm length Palmaz-Schatz stents with activities 0.14 to 23 microCi of 32P were evaluated in animal models of arterial injury and restenosis. The Phase-1 isostent for restenosis intervention study (IRIS trial) was a nonrandomized safety trial designed to evaluate the use of a low activity 32P (0.5 to 1.5 microCi) 15-mm length Palmaz-Schatz stent for the treatment of de novo or restenosis native coronary arterial lesions.. In the porcine coronary restenosis model, at < or =0.5 microCi and > or =3.0 microCi stent activities, there was a 30% reduction in the neointimal and percent area stenosis as compared to nonradioactive stents. The 1.0 microCi stents, however, had nearly 2-fold greater neointimal formation and more luminal narrowing than the control stents. In the Phase 1 IRIS trial, 57 patients with symptomatic de novo or restenosis native coronary lesions have been treated with low activity (0.5 to 1.5 microCi) 32P Palmaz-Schatz coronary stents. Fifty-seven stents were successfully implanted without a major procedural complication (death, urgent coronary bypass, Q-wave myocardial infarction). There were no cases of stent thrombosis, target vessel revascularization, or other adverse events in the first 30 days after implant.. The early clinical results with a low-activity 32P Palmaz-Schatz radioactive stent demonstrate sufficient procedural and 30-day event-free survival to warrant consideration of additional clinical studies to determine the safety and efficacy of this therapy for the prevention of restenosis. Future studies will focus on optimal stent design for delivery of radiation, and will further evaluate safe and effective dosing strategies.

Topics: Animals; Constriction, Pathologic; Phosphorus Radioisotopes; Recurrence; Stents; Swine; Swine, Miniature; Vascular Diseases; Vascular Patency

Topics: Biophysical Phenomena; Biophysics; Combined Modality Therapy; Constriction, Pathologic; Humans; Models, Biological; Phosphorus Radioisotopes; Radiotherapy Planning, Computer-Assisted; Radiotherapy, High-Energy; Stents; Vascular Diseases