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Purpose: We investigated the dose enhancement and internalization of gold nanoparticles (AuNPs) used as a radiosensitizer agent for rotational radiotherapy of breast cancer using a kilovoltage (kV) X‐ray beam. Methods: Human breast cancer cells MDA‐MB‐231 were incubated with or without 100 μg/mL (4.87 nM) or 200 μg/mL (9.74 nM) 15 nm AuNPs and irradiated with 100 kV, 190 kV, or 6 MV X‐rays. To assess the toxicity of the AuNPs, we performed a Sulforhodamine B assay. Using atomic absorption spectroscopy, scanning electron microscopy, transmission electron microscopy, and time‐lapse optical microscopy (rate of 2 frames per minute), we carried out a quantitative assessment of the amount of gold internalized by MDA‐MB‐231 cells and a characterization of the static and dynamical aspects of this internalization process. Results: No effect of AuNPs alone was shown on cell viability. Time‐lapse optical microscopy showed for the first time AuNPs cellular uptake and the dynamics of AuNPs internalization. Electron microscopy demonstrated AuNPs localization in endosomal vesicles, preferentially in the perinuclear region. After irradiation at doses up to 2 Gy, cell survival fraction curves showed increased mortality with AuNPs, with respect to irradiation without AuNPs. The highest effect of radioenhancement by AuNPs (at 9.74 nM AuNPs concentration) was observed at 190 kV showing a dose enhancement factor of 1.33 ± 0.06 (1.34 ± 0.02 at 100 kV), while at 6 MV it was 1.14 ± 0.06. Conclusions: The observed radio‐sensitization effect is promising for future radio‐enhanced kV radiotherapy of breast cancer and quantitatively in the order of previous observations for 15 nm AuNPs. These results of a significant dose enhancement were obtained at 15 nm AuNPs concentration as low as several nanomolar units, at dose levels typical of a single dose fraction in a radiotherapy session. Dynamical behavior of the 3D spatial distribution of 15 nm AuNPs outside the nucleus of single breast cancer cell was observed, with possible implications for future models of AuNPs sensitization. [ABSTRACT FROM AUTHOR]

Objective To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography ( PET)/computed tomography ( CT)-guided radiotherapy ( RT), delivered via helical tomotherapy ( HTT; Tomotherapy® Hi-Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node ( LN) relapses in patients with prostate cancer. Patients and Methods From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline- PET/ CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/ mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline- PET/ CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). Results With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/ mL (hazard ratio [ HR] 3.6, 95% confidence interval [ CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline- PET/ CT-positive LN location ( HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT ( HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs ( HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. Conclusions 11C-choline- PET/ CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients. [ABSTRACT FROM AUTHOR]