Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a 64Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of 64Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from 64Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to 64Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D10 values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that 64Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from 64Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after 64Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that 64Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of 64Cu-ATSM as a cancer treatment modality for hypoxic tumors.

An instrumental method for the individual, sequential or collective measurement of the physical and chemical properties of liquids is presented. A prototype of the fibre drop analyser (FDA), working at only one wavelength in the infrared, has been constructed and tested. The instrument has been used to measure individually surface tension, viscosity, refractive index and the chemical composition of the test solution. The instrument has the capability of simultaneously measuring all of these quantities in one measurement cycle and this possibility is discussed on the basis of one set of results obtained from the sugar processing industry. The instrument is also potentially capable of measuring electrochemical properties of a liquid and some preliminary results are presented. The laboratory FDA has been used to test a series of samples from a large cane sugar manufacturer's process and these measurements demonstrate that the FDA technology has the potential to be used as a remote optrode industrial process monitor for sucrose manufacture, and possibly in other industrial applications.

Macroscopic modeling of singlet oxygen (1O2) is of particular interest because it is the major cytotoxic agent causing biological effects for type II photosensitizers during PDT. We have developed a macroscopic model to calculate reacted singlet oxygen concentration ([1O2]rx for PDT. An in-vivo RIF tumor mouse model is used to correlate the necrosis depth to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include 4 photosensitizer specific photochemical parameters along with the apparent singlet oxygen threshold concentration. Photosensitizer specific model parameters are determined for several type II photosensitizers (Photofrin, BPD, and HPPH). The singlet oxygen threshold concentration is approximately 0.41 – 0.56 mM for all three photosensitizers studied, assuming that the fraction of singlet oxygen generated that interacts with the cell is (f = 1). In comparison, value derived from other in-vivo mice studies is 0.4 mM for mTHPC. However, the singlet oxygen threshold doses were reported to be 7.9 and 12.1 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC and Photofrin PDT, respectively. The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanism on the singlet oxygen threshold dose is discussed using the BPD with different drug-light intervals 3 hrs vs. 15 min. The observed discrepancies between different experiments warrant further investigation to explain the cause of the difference.

Many organ dose calculation tools for computed tomography (CT) scans rely on the assumptions: (1) organ doses estimated for one CT scanner can be converted into organ doses for another CT scanner using the ratio of the Computed Tomography Dose Index (CTDI) between two CT scanners; and (2) helical scans can be approximated as the summation of axial slices covering the same scan range. The current study aims to validate experimentally these two assumptions. We performed organ dose measurements in a 5 year-old physical anthropomorphic phantom for five different CT scanners from four manufacturers. Absorbed doses to 22 organs were measured using thermoluminescent dosimeters for head-to-torso scans. We then compared the measured organ doses with the values calculated from the National Cancer Institute dosimetry system for CT (NCICT) computer program, developed at the National Cancer Institute. Whereas the measured organ doses showed significant variability (coefficient of variation (CoV) up to 53% at 80 kV) across different scanner models, the CoV of organ doses normalised to CTDIvol substantially decreased (12% CoV on average at 80 kV). For most organs, the difference between measured and simulated organ doses was within  ±20% except for the bone marrow, breasts and ovaries. The discrepancies were further explained by additional Monte Carlo calculations of organ doses using a voxel phantom developed from CT images of the physical phantom. The results demonstrate that organ doses calculated for one CT scanner can be used to assess organ doses from other CT scanners with 20% uncertainty (k  =  1), for the scan settings considered in the study.

Photodynamic therapy (PDT) offers a cancer treatment modality capable of providing minimally invasive localized tumor necrosis. To accurately predict PDT treatment outcome based on pre-treatment patient specific parameters, an explicit dosimetry model is used to calculate apparent reacted 1O2 concentration ([1O2]rx) at varied radial distances from the activating light source inserted into tumor tissue and apparent singlet oxygen threshold concentration for necrosis ([1O2]rx, sd) for type-II PDT photosensitizers. Inputs into the model include a number of photosensitizer independent parameters as well as photosensitizer specific photochemical parameters ξ, σ, and β. To determine the specific photochemical parameters of benzoporphyrin derivative monoacid A (BPD), mice were treated with BPD-PDT with varied light source strengths and treatment times. All photosensitizer independent inputs were assessed pre-treatment and average necrotic radius in treated tissue was determined post-treatment. Using the explicit dosimetry model, BPD specific ξ, σ, and β photochemical parameters were determined which estimated necrotic radii similar to those observed in initial BPD-PDT treated mice using an optimization algorithm that minimizes the difference between the model and that of the measurements. Photochemical parameters for BPD are compared with those of other known photosensitizers, such as Photofrin. The determination of these BPD specific photochemical parameters provides necessary data for predictive treatment outcome in clinical BPD-PDT using the explicit dosimetry model.