Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter.

The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET alpha-emitter astatine-211 ((211)At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 ((123)I), 340-fold for technetium-99m pertechnetate ((99m)TcO(4)(-)) and 60-fold for (211)At. Cellular (211)At accumulation was found to be dependent on extracellular Na(+) ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and (99m)TcO(4)(-) uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated (211)At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and (211)At were rapidly (apparent t(1/2) 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times ((123)I), 25 times ((99m)TcO(4)(-)) and 10 times ((211)At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of (123)I and (211)At, respectively, was found in NIS tumours by region of interest analysis ( n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for (123)I, 5.2 h for (211)At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBq(tumour) for (131)I and 50.3 Gy/MBq(tumour) for (211)At). In conclusion, NIS-expressing tumour cell lines of different origin displayed specific radionuclide uptake in vitro and in vivo. We provide first direct evidence that the high-energy alpha-emitter (211)At is efficiently transported by NIS. Application of (211)At may direct higher radiation doses to experimental tumours than those calculated for (131)I. Thus, (211)At may represent a promising alternative radionuclide for future NIS-based tumour therapy.

A water target with beam sweep for routine fluorine-18 production.

Fluorine-18 (18F) production with 18O-enriched water targets is well established world-wide. Heat transfer is still a critical point, however, when high beam currents are used to increase the amount of radioactivity per batch within an adequate irradiation period. The technique of beam sweep formerly used in Hannover for all targets has been adapted for this water target again. A titanium target with a beam sweep of up to 3 cm in the horizontal plane was designed to keep the total amount of enriched water low (2.06 ml), to allow beam currents of 30 microA for 1 h on a daily schedule and thereby to extend maintenance periods to more than 6 months. The design had to take into account that the target must be mounted on a target ladder with five additional positions and that the beam is carried by a 5.50 m beam line from a variable energy, multi-particle cyclotron (mc35, Scanditronix) to the target. The target has been in use for more than 130 consecutive runs with beam currents of about 30 microA at a target pressure of up to 15 bar without any maintenance. The mean value of the recovered radioactivity has reached 91.9+/-7.7% of the theoretically expected value at the end of bombardment (EOB).

Design of gas targets for the production of medically used radionuclides with the help of Monte-Carlo simulation of small angle multiple scattering of charged particles.

Due to scattering of protons or deuterons in the target gas the radius of beams increases with increasing penetration depth of the particles. The increase depends on the kind of beam particle, the energy, the target gas and its temperature and pressure. A Monte-Carlo program was developed for stimulation of multiple scattering. The initial beam has a particle distribution of variable sinusoidal shape behind the entrance window and may be cut off by the simulation of a collimator. The beam distribution is calculated for up to 14 planes representing energy values of the particles due to a predefined range from one plane to the next. The energy loss is calculated with the help of an integrated Bethe-Bloch routine. The distribution of the particles within the plane may be rearranged into profiles and transferred to a spreadsheet for further manipulation and graphical printout. Simulations are carried out for radionuclide production routes, commonly used for position emission tomography (PET).