A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners.
According to the World Health Organization (WHO), at the end of 2020, 7.8 million women alive were diagnosed with breast cancer in the past 5 years, making it the world's most prevalent cancer. It is largely recognized and demonstrated that early detection represents the first strategy to follow in the fight against cancer. The effectiveness of mammography screening for early breast cancer detection has been proven in several surveys and studies over the last three decades. The estimation of the Mean Glandular Dose (MGD) is important to understand the radiation-associated risk from breast x-ray imaging exams. It continues to be the subject of numerous studies and debates, since its accuracy is directly related to risk estimation and for optimizing breast cancer screening programs. This manuscript reviews the main dosimetry formalisms used to estimate the MGD in mammography and to understand the continuing efforts to reduce the absorbed dose over the last forty years. The dosimetry protocols were formulated initially for mammography. Digital breast tomosynthesis (DBT) either in conjunction with synthesized digital mammogram (SDM) or with digital mammography (DM), is routinely used in many breast cancer screening programs and consequently the dosimetry protocols were extended for these techniques.
Despite some progress, the overall survival of patients with glioblastoma (GBM) remains extremely poor. In this context, there is a pressing need to develop innovative therapy strategies for GBM, namely those based on nanomedicine approaches. Towards this goal, we have focused on nanoparticles (AuNP-SP and AuNP-SPTyr8) with a small gold core (ca. 4 nm), carrying DOTA chelators and substance P (SP) peptides. These new SP-containing AuNPs were characterized by a variety of analytical techniques, including TEM and DLS measurements and UV-vis and CD spectroscopy, which proved their high in vitro stability and poor tendency to interact with plasma proteins. Their labeling with diagnostic and therapeutic radionuclides was efficiently performed by DOTA complexation with the trivalent radiometals 67Ga and 177Lu or by electrophilic radioiodination with 125I of the tyrosyl residue in AuNP-SPTyr8. Cellular studies of the resulting radiolabeled AuNPs in NKR1-positive GBM cells (U87, T98G and U373) have shown that the presence of the SP peptides has a crucial and positive impact on their internalization by the tumor cells. Consistently, 177Lu-AuNP-SPTyr8 showed more pronounced radiobiological effects in U373 cells when compared with the non-targeted congener 177Lu-AuNP-TDOTA, as assessed by cell viability and clonogenic assays and corroborated by Monte Carlo microdosimetry simulations.
Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or water as well as the spectral distribution of electrons leaving the GNP. Initially, only the ratio of energy deposition with and without GNP was to be reported. During the evaluation of the exercise, however, the data for energy deposition in the presence and absence of the GNP were also requested. A GNP size of 50 nm and 100 nm diameter was considered as well as two different X-ray spectra (50 kVp and 100kVp). This introduced a redundancy that can be used to cross-validate the internal consistency of the simulation results. In this work, evaluation of the reported results is presented in terms of integral quantities that can be benchmarked against values obtained from physical properties of the radiation spectra and materials involved. The impact of different interaction cross-section datasets and their implementation in the different Monte Carlo codes is also discussed.
Conventional mammography remains the primary imaging modality for state-of-the-art breast imaging practice and its benefit (both on diagnostic and screening) was largely reported. In mammography, the typical Mean Glandular Dose (MGD) from X-ray radiation to the breast spans, on average, from 1 to 10 mGy, depending on breast thicknesses, percentage of fibroglandular tissue, and on the examination purpose. The aim of this narrative review is to describe the extent of radiation risk in X-ray breast imaging and discuss the main steps and parameters (e.g. MGD, screening frequency and number of examination views) that may have an influence on the radiation risk assessment. Even though the radiation doses used with these examinations are very low, as compared to other medical or natural radiation exposures, there is a non-negligible associated risk of radiation-induced cancer. Accurate radiation risk assessment permits to better balance the overall estimation of the benefit-to-risk ratio in X-ray breast imaging. It is expected that a better knowledge about radiation-induced cancer risk among population could improve the communications skills between patients and clinicians and could help to increase the awareness in women about radiation risk perception for a transparent and proper informed choice of imaging exam.