Biomedical subjects

U O Häfeli

Publications and source records attributed to U O Häfeli.

12 recordsLinked to original sources

PubMed2004

Magnetically modulated therapeutic systems.

Magnetically targeted drug delivery by particulate carriers is an efficient method of delivering drugs to localized disease sites, such as tumors. High concentrations of chemotherapeutic or radiological agents can be achieved near the target site without any toxic effects to normal surrounding tissue. Non-targeted applications of magnetic microspheres and nanospheres include their use as contrast agents (MRI) and as drug reservoirs that can be activated by a magnet applied outside the body. Historic and current applications of magnetic microspheres will be discussed, as well as future directions and problems to be overcome for the efficient and beneficial use of magnetic carriers in clinical practice. More information about the field and an extensive bibliography is available at "."

Animals↗

PubMed2004

Magnetizable needles and wires--modeling an efficient way to target magnetic microspheres in vivo.

The in vivo targeting of tumors with magnetic microspheres is currently realized through the application of external non-uniform magnetic fields generated by rare-earth permanent magnets or electromagnets. Our theoretical work suggests a feasible procedure for local delivery of magnetic nano- and microparticles to a target area. In particular, thin magnetizable wires placed throughout or close to the target area and magnetized by a perpendicular external uniform background magnetic field are used to concentrate magnetic microspheres injected into the target organ's natural blood supply. The capture of the magnetic particles and the building of deposits thereof in the blood vessels of the target area were modeled under circumstances similar to the in vivo situation. This technique could be applied to magnetically targeted cancer therapy or magnetic embolization therapy with magnetic particles that contain anticancer agents, such as chemotherapeutic drugs or therapeutic radioisotopes.

Antineoplastic Agents↗

PubMed2001

Stability of biodegradable radioactive rhenium (Re-186 and Re-188) microspheres after neutron-activation.

Our objective was to determine if microspheres made from the biodegradable polymer poly(lactic acid) that contained rhenium could withstand the conditions of direct neutron activation necessary to produce therapeutic amounts of radioactive rhenium. The radiation damage of the polymer produced by gamma-doses of up to 1.05 MGy from Re-186 and Re-188 was examined by scanning electron microscopy and size exclusion chromatography. At a thermal neutron flux of 1.5 x 10(13)n/cm2/s the microspheres melted after 3 h in the nuclear reactor, but suffered little damage after 1 h of radiation and released less than 5% of the radioactivity during incubation in buffer at 37 degrees C. The radioactive microspheres produced in this manner have a specific activity too low for radioembolization for treatment of liver tumors, but could be injected directly into tumors or applied topically to the wound bed of partially resected tumors.

Biodegradation, Environmental↗

PubMed2001

Self-absorption correction for 32P, 198Au and 188Re stents: dose point kernel calculations versus Monte Carlo.

Monte Carlo simulations of dose distributions around radioactive stents are very time intensive. Thus, in order to calculate the dose distribution around a 188Re stent, we chose to test a point kernel method, a method which is known to be faster but the accuracy of which has not been established for this application. The dose point kernel method, which takes into account absorption in the strut material (=self-absorption), was based on different beta-emitting point source distributions in water by itself and surrounded by steel spheres of different thicknesses. This information was input into an integration routine that modeled either a Palmaz-Schatz or Multilink stent. The dose distributions around 198Au and 32P stents calculated with the dose point kernel method were compared to those calculated using EGS4 and MCNP 4B Monte Carlo methods. The resulting correction for self-absorption in steel was distance dependent and averaged 1.12 for 32P and 1.25 for 198Au stents. The dose point kernel method gave nearly identical results to these full Monte Carlo simulations and was thus used to calculate the dose distributions around a 188Re stent. Although 188Re has a half-life of only 17 hours, it is posited to be useful for radioactive restenosis prevention, given that a recently developed rapid electrodeposition procedure allows stents to be made radioactive, at predetermined activities, within 15 minutes. The dose point kernel calculations of a 188Re-coated Multilink stent were compared to its radiochromic film measurements. The dose fall-off agreed with the calculations within 5% over 0.4 to 3.5 mm from the stent surface. The dose point kernel method is a valuable tool to determine depth dose distributions around activated stents taking into account the detailed geometry and the self-absorption in the struts. It not only requires much less processing time than Monte Carlo methods, but also allows the use of higher resolutions in modeling the geometry, which leads to more accurate self-absorption correction factors.

Angioplasty, Balloon, Coronary↗

PubMed2000

Dosimetry of a W-188/Re-188 beta line source for endovascular brachytherapy.

PURPOSE: The objective was to determine the dosimetry of a potential endovascular brachytherapy source consisting of a coiled tungsten wire mounted on the distal end of a drive wire and neutron-activated to contain the parent-daughter nuclides tungsten-188 (188W) and rhenium-188 (188Re). METHODS: A coiled tungsten wire 40 mm in length was neutron-activated by double-neutron capture for 78 hours at 1.9 x 10(15) h/cm2/s to contain 925 MBq (25 mCi) of 188W/188Re in equilibrium. The dose-fall off from this source was determined using three independent methods: (a) Thermoluminescence dosimetry with small LiF-100 rods, (b) Gafchromic film dosimetry, and (c) Bang gel dosimetry. In addition, a Monte Carlo simulation was performed to compute the beta-dose. RESULTS: Each of the three measurement methods recorded similar values for the dose fall-off within the distances useful for endovascular brachytherapy. The Monte Carlo calculations closely approximated the measured results in the treatment range between 1 and 3 mm and may thus be useful for evaluating changing geometries in the development of catheters and source setups. A 2 min restenosis treatment delivering 20 Gy at a radius of 2 mm would require a source of 1384.8 MBq/cm (37.4 mCi/cm). CONCLUSIONS: The dose distribution from a 188W/188Re source is similar to that of a 90Y-source. An added advantage of the 188W/188Re source is that it can be used for at least two months and still provides fast treatment times because of the parent isotope's half-life of 69 days. The additional gamma emission from the source is too small to impose a serious radiological hazard. The high atomic number and density of the source material allows direct fluoroscopic imaging without additional markers.

Beta Particles↗

PubMed1999

Parenchymal cell proliferation in coronary arteries after percutaneous transluminal coronary angioplasty: a human tissue bank study.

PURPOSE: Restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains a limitation of this technique. Arterial wall cell proliferation is a component of restenosis preventable with intravascular brachytherapy. This study attempts to locate the sites of cellular proliferation after PTCA so as to aid the optimization of this therapy. METHODS AND MATERIALS: Autopsy records from January 1, 1985 through December 31, 1995 were reviewed, and 27 patients who received PTCA prior to death were identified who also had evidence of PTCA on histologic examination of the arterial sections. The sections were subjected to immunohistochemical staining for proliferating cell nuclear antigen (PCNA) to detect the proliferating cells in the arterial sections, followed by image analysis to determine the proliferative index (PI) of all regions and layers of the section. RESULTS: The PI did not differ significantly according to vessel region (plaque, plaque shoulder, or portion of vessel wall with lowest plaque burden), vessel layer (intima, media, adventitia), or evidence of prior PTCA. There was a trend toward a higher PI in young lesions. CONCLUSION: Cell proliferation in the vascular wall after PTCA was found throughout the treated arterial section's axial plane, not only in the periluminal region.

Angioplasty, Balloon, Coronary↗

PubMed1999

Hepatic tumor radioembolization in a rat model using radioactive rhenium (186Re/188Re) glass microspheres.

PURPOSE: The aim of this study was to fully characterize newly developed radioactive rhenium glass microspheres in vivo by determining their biodistribution, stability, antitumor effect, and toxicity after hepatic arterial injection in a syngeneic rat hepatoma model. The dose response of the tumors to increasing amounts of radioactive 186Re and 188Re microspheres was also determined. METHODS AND MATERIALS: Rhenium glass microspheres were made radioactive by neutron activation and then injected into the hepatic artery of Sprague-Dawley rats containing 1-week-old Novikoff hepatomas. The biodistribution of the radioactivity and tumor growth were determined 1 h and 14 days after injection. RESULTS: Examination of the biodistribution indicated a time-dependent, up to 7-fold increase in Novikoff hepatoma uptake as compared to healthy liver tissue uptake. After 14 days, the average T:L ratio was 1.97. Tumor growth in the rats receiving radioactive microspheres was significantly lower than in the group receiving nonradioactive microspheres (142% vs. 4824%, p = 0.048). Immediately after injection, 0.065% of the injected radioactivity was measured in the thyroid; it decreased to background levels within 24 h. CONCLUSION: Radioactive rhenium microspheres are effective in diminishing tumor growth without altering hepatic enzyme levels. The microspheres are safe with respect to their radiation dose to healthy tissue and radiation release in vivo and can be directly imaged in the body with a gamma camera. Furthermore, rhenium microspheres have an advantage over pure beta-emitting microspheres in terms of preparation and neutron-activation time. In sum, this novel radiopharmaceutical may provide an innovative and cost-effective approach for the treatment of nonresectable liver cancer.

Animals↗

PubMed1998

Preparation and properties of radioactive rhenium glass microspheres intended for in vivo radioembolization therapy.

Rhenium glass microspheres composed of metallic rhenium particles dispersed within a magnesium alumino borate glass matrix were produced by sintering ReO2 powder and glass frit at 1050 degrees C. The in vitro chemical durability of radioactive and nonradioactive microspheres was determined from chemical corrosion tests on microspheres immersed in phosphate-buffered saline (PBS) solution at 37 degrees C. The dosimetric properties of these microspheres also were calculated. The rhenium glass microspheres are chemically durable in body fluids and release < 1.2% of radioactive rhenium after being immersed in PBS solution for 32 days at 37 degrees C. Therapeutic radioactive rhenium activities can be obtained in < 10 h by neutron activation of these microspheres in a thermal neutron flux of 8 x 10(13) cm(-2)s(-1). A 50 mg injection of radioactive rhenium glass microspheres containing 3.7 GBq of 186Re and 8.5 GBq of 188Re could deliver a 100 Gy dose to a cancerous liver while limiting the total body dose from rhenium dissolution in vivo to approximately 1 mGy.

Biocompatible Materials↗

PubMed1998

Electrodeposition of radioactive rhenium onto stents to prevent restenosis.

Radioactive stents are currently being evaluated for preventing restenosis. A major difficulty to overcome is the need to load any pre-manufactured stents with defined amounts of radioactivity at the time of use. Using stents that are preloaded by the manufacturer is not ideal because the stent length usually differs from the length needed for a specific lesion and the amounts of radioactivity varies widely due to ongoing decay of the source. Thus, we have developed a novel method that allows any currently used stainless steel or tantalum stent to be coated with radioactive rhenium. The method involves placing the stent in a series of rinsing and electroplating solutions, one containing radioactive rhenium (186Re, 188Re, or both). The overall processing time is 15 min and the procedure may be conveniently applied just prior to the stent insertion. The plated stent contains radioactive rhenium in a 1.2 microm-thick cobalt layer, with an outer 2 microm layer of gold. The gold layer gives the radioactive stent excellent radiochemical stability, good bending and biocompatibility properties, and improves stent visibility during fluoroscopy.

Angioplasty, Balloon, Coronary↗

PubMed1995

Effective targeting of magnetic radioactive 90Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results.

Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter 90Y were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the 90Y magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with 90Y-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as 90Y-microspheres show great promise for regional or intracavitary radiotherapy.

Animals↗

PubMed1994

Magnetically directed poly(lactic acid) 90Y-microspheres: novel agents for targeted intracavitary radiotherapy.

High energy beta-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. We developed as carriers for the ionic form of 90Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe3O4 (magnetite) which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10-40 microns MMS were radiochemically loaded to high specific activity with 90Y at a pH of 5.7. Stability studies showed that approximately 95% of added 90Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 degrees C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. We are currently optimizing this system for use in the treatment of neoplastic meningitis.

Animals↗

PubMedDate not supplied

Preparation and characterization of radioactive Co/188Re stents intended for lung cancer treatment using an electrodeposition method.

A procedure for electroplating a Co/(188)Re alloy layer on metal coils (stents) at room temperature was developed. The electroplating of the Co/(188)Re alloy layer was carried out at a current density of 93 A m(-2) and produced a physically strong Co/(188)Re alloy layer that adhered well to a thin gold strike layer on top of the stent material. The final gold layer was also stable. An empirically-found equation correlates the radioactive electroplating efficiency factor to the concentration of the radioisotope and was used to deposit predetermined amounts of radioactivity on the stent surface. Radioactive stents can be prepared and quality control performed within 2 hours using an automated electroplater and dosimetric quality control system. The radioactivity was homogeneously distributed on the stent surface. The in vitro stability in human plasma at 37 degrees C was found to be greater than 95% for both Wallstent and Ultraflex stent after 72 hours of incubation. A clinical pilot trial is planned after successful completion of animal testing.

Brachytherapy↗