Alpha and beta particulate radiation are used for non-treated neoplasia, due to their ability to reach and remain in tumor sites. Radium-223 (²²³Ra), an alpha emitter, promotes localized cytotoxic effects, while radioactive gold (¹⁹⁸Au), beta-type energy, reduces radiation in the surrounding tissues. Nanotechnology, including several radioactive nanoparticles, can be safely and effectively used in cancer treatment. In this context, this study aims to analyze the antitumoral effects of [²²³Ra]Ra nanomicelles co-loaded with radioactive gold nanoparticles ([¹⁹⁸Au]AuNPs). For this, we synthesize and characterize nanomicelles, as well as analyze some parameters, such as particle size, radioactivity emission, dynamic light scattering, and microscopic atomic force. [²²³Ra]Ra nanomicelles co-loaded with [¹⁹⁸Au]AuNPs, with simultaneous alpha and beta emission, showed no instability, a mean particle size of 296 nm, and a PDI of 0.201 (±0.096). Furthermore, nanomicelles were tested in an in vitro cytotoxicity assay. We observed a significant increase in tumor cell death using combined alpha and beta therapy in the same formulation, compared with these components used alone. Together, these results show, for the first time, an efficient association between alpha and beta therapies, which could become a promising tool in the control of tumor progression.

The use of alpha-particle (α-particle) radionuclides, especially [²²³Ra]RaCl₂ (radium dichloride), for targeted alpha therapy is steadily increasing. Despite the positive clinical outcomes of this therapy, very little data are available about the effect on the ultrastructure of cells. The purpose of this study was to evaluate the nanomechanical and ultrastructure effect of [²²³Ra] RaCl₂ on cancer cells. To analyze the effect of [²²³Ra]RaCl₂ on tumor cells, human breast cancer cells (lineage MDA-MB-231) were cultured and treated with the radiopharmaceutical at doses of 2 µCi and 0.9 µCi. The effect was evaluated using atomic force microscopy (AFM) and transmission electron microscopy (TEM) combined with Raman spectroscopy. The results showed massive destruction of the cell membrane but preservation of the nucleus membrane. No evidence of DNA alteration was observed. The data demonstrated the formation of lysosomes and phagosomes. These findings help elucidate the main mechanism involved in cell death during α-particle therapy.

Losartan is widely used in clinics to treat cardiovascular related diseases by selectively blocking the angiotensin II type 1 receptors (AT₁Rs), which regulate the renin-angiotensin system (RAS). Therefore, monitoring the physiological and pathological biodistribution of AT₁R using positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS. Herein, we describe the synthesis and characterization of two novel losartan derivatives PET tracers, [¹⁸F]fluoroethyl-losartan ([¹⁸F]FEtLos) and [¹⁸F]ammoniomethyltrifluoroborate-losartan ([¹⁸F]AMBF₃Los). [¹⁸F]FEtLos was radiolabeled by ¹⁸F-fluoroalkylation of losartan potassium using the prosthetic group 2-[¹⁸F]fluoroethyl tosylate; whereas [¹⁸F]AMBF₃Los was prepared following an one-step ¹⁸F-¹⁹F isotopic exchange reaction, in an overall yield of 2.7 ± 0.9% and 11 ± 4%, respectively, with high radiochemical purity (>95%). Binding competition assays in AT₁R-expressing membranes showed that AMBF₃Los presented an almost equivalent binding affinity (K_i 7.9 nM) as the cold reference Losartan (K_i 1.5 nM), unlike FEtLos (K_i 2000 nM). In vitro and in vivo assays showed that [¹⁸F]AMBF₃Los displayed a good binding affinity for AT₁R-overexpressing CHO cells and was able to specifically bind to renal AT₁R. Hence, our data demonstrate [¹⁸F]AMBF₃Los as a new tool for PET imaging of AT₁R with possible applications for the diagnosis of cardiovascular, inflammatory and cancer diseases.

A global need exists for new and more effective contrast agents for computed tomography and traditional X-ray modalities. Among the few options available nowadays, limitations imposed by industrial production, performance, and efficacy restrict the use and reduce the potential of both imaging techniques. The use of nanomaterials as new contrast agents for X-ray and computed tomography is an innovative and viable way to increase the options and enhance performance. In this study, we evaluated eight nanomaterials: hydroxyapatite doped with zinc (Zn-HA 10%); hydroxyapatite doped with strontium (Sr-HA 10%); hydroxyapatite without thermal treatment (HA 282 STT); thermally treated hydroxyapatite (HA 212 500 °C and HA 01.256 CTT 1000 °C); hydroxyapatite microspheres (HA microspheres); gold nanoparticles (AuNP); and graphene oxide doped with copper (Cu-GO). The results showed that for both imaging modalities; HA microspheres were the best option, followed by hydroxyapatite thermally treated at 1000 °C. The nanomaterials with the worst results were hydroxyapatite doped with zinc (Zn-HA 10%), and hydroxyapatite doped with strontium (Sr-HA 10%). Our data demonstrated the potential of using nanomaterials, especially HA microspheres, and hydroxyapatite with thermal treatment (HA 01.256 CTT 1000 °C) as contrast agents for X-ray and computed tomography.

Background: 2-[¹⁸F]Fluoroethyltosylate ([¹⁸F]FEtOTs) is a well-known¹⁸F-fluoroalkylating agent widely used to synthesize radiotracers for positron emission tomography. The widespread use of [¹⁸F]FEtOTs is due in part to its low volatility when compared to other halide and sulfonate building blocks. In this work, the radioactive volatile side-products formed during the synthesis of [¹⁸F]FEtOTs were identified and characterized for the first time, and an optimization of the reaction conditions to minimize their formation was proposed.Results: In order to characterize the volatiles produced during [¹⁸F]FEtOTs synthesis, the reaction mixtures of both cold FEtOTs and [¹⁸F]FEtOTs were co-injected onto the HPLC system. The radioactive peaks corresponding to the volatile compounds were collected, analyzed through headspace gas chromatography mass spectrometry sampler (HS-GC–MS) and identified as vinyl fluoride ([¹⁹F]VF) and 2-fluoroethanol ([¹⁹F]FEOH). By using a rotatable central composite design with a two-level full factorial core of two factors (2²), it was determined that temperature and time are independent variables which affect the generation of [¹⁸F]VF and [¹⁸F]FEOH during the radiosynthesis of [¹⁸F]FEtOTs. In addition, in order to reduce the formation of the volatiles ([¹⁸F]VF and [¹⁸F]FEOH) and increase the yield of [¹⁸F]FEtOTs, it was demonstrated that the molar ratio of base to precursor must also be considered.Conclusion: [¹⁸F]VF and [¹⁸F]FEOH are volatile side-products formed during the radiosynthesis of [¹⁸F]FEtOTs, whose yields depend on the reaction time, temperature, and the molar ratio of base to precursor. Therefore, special care should be taken during the radiosynthesis and subsequent reactions using [¹⁸F]FEOTs in order to avoid environmental contamination and to improve the yield of the desired products.