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Purpose Ra-223, an α-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metasteses of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. Methods The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. Results The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histograms results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e., the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 Gy to 20 Gy. Conclusion The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the absorbed fraction method of dose calculation.

We present the synthesis and characterization of a highly efficient thorium chelator, derived from the octadentate hydroxypyridinone class of compounds. The chelator forms extremely stable complexes with fast formation rates in the presence of Th-227 (ambient temperature, 20min). In addition, mouse biodistribution data are provided which indicate rapid hepatobiliary excretion route of the chelator which, together with low bone uptake, supports the stability of the complex in vivo. The carboxylic acid group may be readily activated for conjugation through the ɛ-amino groups of lysine residues in biomolecules such as antibodies. This chelator is a critical component of a new class of Targeted Thorium Conjugates (TTCs) currently under development in the field of oncology.

Several nitrated polycyclic aromatic hydrocarbons (nitro-PAH) are direct-acting mutagens and/or carcinogens, and are important constituents of combustion emissions and ambient air. These nitro-PAH are emitted from various combustion sources including gasoline and diesel engine exhaust, aluminium smelting effluent, coal fly ash, wood smoke, and cigarette smoke condensates. Of these, diesel engine exhaust is the best characterized, more than 50 nitrated polycyclic aromatic compounds having been identified by Paputa-Peck et al., including 1-nitropyrene (1-NP) as the single most abundant nitro-PAH. However, nitro-PAH may also be formed during source-receptor transport by atmospheric reactions of adsorbed or gas-phase PAH with oxides of nitrogen, nitric acid and other atmospherically important species such as the OH radical. Evidence for the atmospheric formation of nitro-PAH has come only recently, from observations that 2-nitropyrene (2-NP) and 2-nitrofluoranthene (2-NF) neither of which has been reported to be emitted from combustion sources, are among the major nitro-PAH present in ambient air. We present here data from several locations which demonstrate that these two atmospherically formed nitro-PAH are ubiquitous in tropospheric ambient air.