Open low-field magnetic resonance imaging in radiation therapy treatment planning.

PURPOSE: To evaluate the possibilities of an open low-field magnetic resonance imaging (MRI) scanner in external beam radiotherapy treatment (RT) planning. METHODS AND MATERIALS: A custom-made flat tabletop was constructed for the open MR, which was compatible with standard therapy positioning devices. To assess and correct image distortion in low-field MRI, a custom-made phantom was constructed and a software algorithm was developed. A total of 243 patients (43 patients with non-small-cell lung cancer, 155 patients with prostate cancer, and 45 patients with brain tumors) received low-field MR imaging in addition to computed tomographic (CT) planning imaging between January 1998 and September 2001 before the start of the irradiation. RESULTS: Open low-field MRI provided adequate images for RT planning in nearly 95% of the examined patients. The mean and the maximal distortions 15 cm around the isocenter were reduced from 2.5 mm to 0.9 mm and from 6.1 mm to 2.1 mm respectively. The MRI-assisted planning led to better discrimination of tumor extent in two-thirds of the patients and to an optimization in lung cancer RT planning in one-third of the patients. In prostate cancer planning, low-field MRI resulted in significant reduction (40%) of organ volume and clinical target volume (CTV) compared with CT and to a reduction of the mean percentage of rectal dose of 15%. In brain tumors, low-field MR image quality was superior compared with CT in 39/45 patients for planning purposes. CONCLUSIONS: The data presented here show that low-field MRI is feasible in RT treatment planning when image correction regarding system-induced distortions is performed and by selecting MR imaging protocol parameters with the emphasis on adequate images for RT planning.

Transient DNA double-strand breakage in 4-hydroperoxyifosfamide-treated mammalian cells in vitro does not interact with the rejoining of radiation-induced double-strand breaks.

BACKGROUND: 4-Hydroxyifosfamide is the primary metabolite in vivo of the bifunctional alkylating cytostatic ifosfamide. DNA interstrand cross-linking induced by bifunctional alkylators may be repaired through an intermediate with unligated repair patches on both strands which should uncover analytically as DNA double-strand breaks and allow to measure the rejoining kinetic of this repair intermediate. Additionally, the combined effects of drug and radiation treatment on rejoining of double-strand breaks was investigated with two different mammalian cell lines. MATERIAL AND METHODS: V79 (rodent fibroblasts) and Widr (human colon carcinoma) cells were treated for 2 hours with 4-hydroperoxyifosfamide which rapidly decays to 4-hydoxyifosfamide in aqueous solution or were exposed in combination with ionizing radiation followed by incubation for repair with or without the drug. DNA double-strand breakage was measured by pulsed-field electrophoresis. RESULTS: The 2 hours 4-hydroperoxyifosfamide treatment (30 micrograms/ml) resulted in a pronounced DNA fragmentation that, 2-4 hours after drug removal, declined with an estimated half-live of about 4 hours for both cell lines. When the cells were additionally irradiated with 10 Gy given in the middle of drug exposure, the residual fragmentation after 12 or 24 hours incubation for repair was only marginally increased, roughly corresponding to the respective value after radiation, alone. A continuous drug exposure of 6 hours (at 10 micrograms/ml) resulted in a fragmentation that was independent of a preirradiation with a high dose of 30 Gy, immediately before drug addition. CONCLUSIONS: The present data support the idea that unligated/unrejoined double-stranded DNA ends are generated during the repair of lesions from bifunctional alkylators. The rate of subsequent rejoining is in the order of magnitude of the slow rejoining of radiation-induced double-strand breaks. Processing of double-stranded DNA damage from either 4-hydroperoxyifosfamid or radiation exposure is apparently unaffected in combined treatments.

Interaction of pemetrexed disodium (ALIMTA, multitargeted antifolate) and irradiation in vitro.

PURPOSE: Pemetrexed disodium (Alimta, multitargeted antifolate, LY231514; Eli Lilly and Co., Indianapolis, Indiana) ("pemetrexed") is a new folate antimetabolite with significant antitumor activity. Different from classic antifolates, pemetrexed inhibits several key enzymes of thymidylate and purine synthesis, but a radiosensitizing potential may also be presumed. Therefore, the interaction of pemetrexed and ionizing radiation was studied for in vitro clonogenic survival of different human tumor cell lines. METHODS AND MATERIALS: Human colon (Widr), breast (MCF-7), cervix (Hela), and lung (LXI) carcinoma cells from log-phase cultures were exposed to pemetrexed (2 h) in combination with different radiation doses given 1 h before pemetrexed washout (all cell lines) or at different points of time before or after pemetrexed addition (Widr). Survival curves were analyzed according to the linear-quadratic (LQ) model, and mean inactivation doses (MID) and radiation enhancement ratios were calculated from the survival curve parameters. Cell-cycle progression of serum-stimulated and pemetrexed- or mock-treated Widr cells was monitored by flow cytometry. RESULTS: Radiosensitization was found for all cell lines at moderately toxic pemetrexed exposures (0.05-0.3 microg/ml [106-636 nM]), but this was cell-type dependent and was most pronounced at roughly isotoxic concentrations, for the least pemetrexed-sensitive Widr cells. Enhancement ratios ranged from about 1.2 (MCF-7 and Hela) to 1.8 (Widr), with a tendency to increase with pemetrexed concentration. Little, if any, change of radiosensitization was observed (Widr) when the time of irradiation was varied from 4 h before to 10 h after the beginning of pemetrexed treatment. Cell-cycle progression of serum-stimulated Widr cells was only marginally affected by pemetrexed. CONCLUSIONS: Pemetrexed enhances radiation-induced cell inactivation at moderately toxic exposures and over many hours after drug removal. This effect is not due to disturbed cell-cycle progression, but likely involves an interaction of pemetrexed with long-lived (>4 h) cellular radiation damage and needs to be considered when introducing a combined clinical application.