Enhanced phosphatidylserine-selective cancer therapy with irradiation and SapC-DOPS nanovesicles.

Normal living cells exhibit phosphatidylserine (PS) primarily within the intracellular leaflet of the plasma membrane. In contrast, viable cancer cells have high levels of PS on the external surface, and exhibit a broad range of surface PS, even within specific types of cancer. Agents that target surface PS have recently been developed to treat tumors and are expected to be more effective with higher surface PS levels. In this context, we examined whether surface PS is increased with irradiation. In vitro irradiation of cancer cell lines selected surviving cells that had higher surface PS in a dose- and time-dependent manner. This was more pronounced if surface PS was initially in the lower range for cancer cells. Radiation also increased the surface PS of tumor cells in subcutaneous xenografts in nude mice. We found an inverse relationship between steady state surface PS level of cancer cell lines and their sensitivity to radiation-induced cell death. In addition, serial irradiation, which selected surviving cells with higher surface PS, also increased resistance to radiation and to some chemotherapeutic drugs, suggesting a PS-dependent mechanism for development of resistance to therapy. On the other hand, fractionated radiation enhanced the effect of a novel anti-cancer, PS-targeting drug, SapC-DOPS, in some cancer cell lines. Our data suggest that we can group cancer cells into cells with low surface PS, which are sensitive to radiation, and high surface PS, which are sensitive to SapC-DOPS. Combination of these interventions may provide a potential new combination therapy.

A comparison of HDR near source dosimetry using a treatment planning system, Monte Carlo simulation, and radiochromic film.

This study aimed to investigate the high-dose rate Iridium-192 brachytherapy, including near source dosimetry, of a catheter-based applicator from 0.5mm to 1cm along the transverse axis. Radiochromic film and Monte Carlo (MC) simulation were used to generate absolute dose for the catheter-based applicator. Results from radiochromic film and MC simulation were compared directly to the treatment planning system (TPS) based on the American Association of Physicists in Medicine Updated Task Group 43 (TG-43U1) dose calculation formalism. The difference between dose measured using radiochromic film along the transverse plane at 0.5mm from the surface and the predicted dose by the TPS was 24%±13%. The dose difference between the MC simulation along the transverse plane at 0.5mm from the surface and the predicted dose by the TPS was 22.1%±3%. For distances from 1.5mm to 1cm from the surface, radiochromic film and MC simulation agreed with TPS within an uncertainty of 3%. The TPS under-predicts the dose at the surface of the applicator, i.e., 0.5mm from the catheter surface, as compared to the measured and MC simulation predicted dose. MC simulation results demonstrated that 15% of this error is due to neglecting the beta particles and discrete electrons emanating from the sources and not considered by the TPS, and 7% of the difference was due to the photon alone, potentially due to the differences in MC dose modeling, photon spectrum, scoring techniques, and effect of the presence of the catheter and the air gap. Beyond 1mm from the surface, the TPS dose algorithm agrees with the experimental and MC data within 3%.

A Monte Carlo brachytherapy study for dose distribution prediction in an inhomogeneous medium.

The purpose of this study was to present a theoretical analysis of how the presence of bone in interstitial brachytherapy affects dose rate distributions. This study was carried out using a Monte Carlo simulation of the dose distribution in homogeneous medium for 3 commonly used brachytherapy seeds. The 3 seeds investigated in this study are iridium-192 (192Ir) iodine-125 (125I), and palladium-103 (103Pd). The computer code was validated by comparing the specific dose rate (Lambda), the radial dose function g(r), and anisotropy function F(r,theta;) for all 3 seeds with the AAPM TG-43 dosimetry formalism and current literature. The 192Ir seed resulted in a dose rate of 1.115 +/- 0.001 cGy-hr(-1)-U(-1), the 125I seed resulted in a dose rate of 0.965 +/- 0.006 cGy/h(-1)/U(-1), and the 103Pd seed resulted in a dose rate of 0.671 +/- 0.002 cGy/h(-1)/U(-1). The results for all 3 seeds are in good agreement with the AAPM TG-43 and current literature. The validated computer code was then applied to a simple inhomogeneous model to determine the effect bone has on dose distribution from an interstitial implant. The inhomogeneous model showed a decrease in dose rate of 2% for the 192Ir, an increase in dose rate of 84% for 125I, and an increase in dose rate of 83% for the 103Pd at the surface of the bone nearest to the source.

Efficacy of brachytherapy for prostate cancer in African Americans compared with Caucasians.

PURPOSE: To compare the biochemical response to prostate brachytherapy between African Americans and Caucasians in a consecutive series of patients treated at a single institution. METHODS AND MATERIALS: Between July 1995 and October 2001, 173 patients were treated with permanent (125)I seed implantation alone for presumed localized adenocarcinoma of the prostate. Twelve patients were African American and their biochemical response to treatment was compared with the 161 Caucasian patients. The patients were evaluated for biochemical recurrence according to the ASTRO consensus statement and for achieving and maintaining PSA nadirs of < or = 1.0, < or = 0.5, and < or = 0.2. Median pretreatment PSA level was 8 for the African American group and 6 for the Caucasian group. Median Gleason score for each group was 6 and no patients had palpable extraprostatic disease at the time of treatment. RESULTS: None of the African American patients have experienced biochemical recurrence compared with 7.5% of the Caucasian patients (p=0.34). The percentage of African American patients achieving and maintaining a PSA level of < or = 1.0 was 83% compared with 89% for the Caucasian patients (p=0.61). PSA nadir of < or = 0.5 was achieved in 75% of the African American patients and 81% of the Caucasian patients (p=0.52) and 50% of the African American patients experienced PSA levels of < or = 0.2 compared with 59% of the Caucasian patients (p=0.88). CONCLUSION: African American patients with prostate cancer have in general been reported to have worse prognosis compared with Caucasians. This series suggests similar outcome between African American and Caucasian patients treated with brachytherapy for prostate cancer.

Monte Carlo calculations of dose distribution for intramural delivery of radioisotopes using a direct injection balloon catheter.

PURPOSE: A unique method of delivering radiation dose to the coronary vessel wall to prevent restenosis is by direct injection of radioactive compounds into the vessel wall using a specially designed angioplasty balloon catheter. The radiation dose distribution resulting from such intramural delivery was investigated using Monte Carlo simulations. MATERIALS AND METHODS: The radioisotope source distribution was modeled for two configurations within the vessel wall: (1) uniform to a depth of 0.5 mm and (2) confined to discrete pools surrounding the delivery injection ports. Monte Carlo MCNP4B computer simulations were utilized to estimate the associated radiation dose distribution for the following radioisotopes: 188Re, 186Re, 32P, 153Sm, 111In, 123I, and 99mTc. RESULTS: For the uniform case where the radioisotopes are distributed uniformly to the depth of 0.5 mm into the vessel wall, an essentially constant radiation dose is delivered within the source distribution. Outside of the source volume, the dose falls off at a rate depending on the emission properties of the particular radioisotope. The nonuniform case involving discrete pools of activity showed the dose distribution being confined largely to the regions surrounding the delivery ports with significant regions between these ports receiving very little dose. CONCLUSIONS: Direct injection of selected radioisotopes into the arterial wall appears to represent a potentially effective method for delivering radiation dose for the prevention of restenosis. Sufficiently high doses may be obtained from relatively low activity and the dose falls off rapidly outside of the target area for certain radioisotopes.