Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider

Gallium-68 was applied for positron emission tomography (PET) imaging already in the early beginnings of PET imaging. Today, with the introduction of PSMA-targeting tracers (e.g. PSMA-11, PSMA-617, and PSMA-I&T), the number of clinical applications of 68Ga-radiopharmaceuticals for diagnostic imaging has grown considerably. This development was initiated and supported already in the mid-2000s by the commercial availability of 68Ge/68Ga generators designed for clinical usage. This progression was accompanied by the development of several purification methods to generator eluate as well as sophisticated 68Ga-radiopharmaceuticals. Due to the 68Ga-rush, the need for implementation of gallium-68 (depending on production route) and its certain tracers into the pharmacopeia increased. Based on the specifications given by the pharmacopeia, interest focused on the development of automated synthesis systems, 99mTc-analog kits with regard to patient as well as operator safety

The light-oxygen effect in biological cells enhanced by highly localized surface plasmon-polaritons

Here at the first time we suggested that the surface plasmon-polariton phenomenon which it is well described in metallic nanostructures could also be used for explanation of the unexpectedly strong oxidative effects of the low-intensity laser irradiation in living matters (cells, tissues, organism). We demonstrated that the narrow-band laser emitting at 1265 nm could generate significant amount of the reactive oxygen species (ROS) in both HCT116 and CHO-K1 cell cultures. Such cellular ROS effects could be explained through the generation of highly localized plasmon-polaritons on the surface of mitochondrial crista. Our experimental conditions, the low-intensity irradiation, the narrow spectrum band (<4 nm) of the laser and comparably small size bio-structures (~10 μm) were shown to be sufficient for the plasmon-polariton generation and strong laser field confinement enabling the oxidative stress observed

The photobiomodulation of vital parameters of the cancer cell culture by low dose of near-IR laser irradiation

The mechanisms underlining the cell adaptive and/or activating oxidative stress, called low level light or photobiomodulation therapies (PBMT), still remain unclear for the near-infrared spectrum range (750-3000 nm), especially for the 1265-1270 nm range (highest absorption by molecular oxygen). It is most probable that the mitochondria may also appear to be the main target for these wavelengths. It is known that mitochondria can generate ROS under visible and 800-1060 nm spectrum range irradiation, which in turn control voltage-dependent anion channels (VDAC). Here we investigated cellular damage regarding VDAC activity, level of oxidative stress, malondialdehyde content, cell viability, mitochondrial potential and mass, GSH level, mitochondrial and nuclear DNA damage in the cancer cell culture exposed to low-level laser irradiation at 1265 nm. We used a continuous wave laser with output power 4 mW; the energy densities employed were 0.3-9.45 J/cm 2. We observed that the laser radiation at 1265 nm can induce the oxidative stress, enhance apoptosis, and disturb mitochondrial functioning at the energy density of 9.54 J/cm 2. In addition, inhibition of VDAC enhances the observed effects. It has been shown that the laser irradiation at 1265 nm damages mitochondrial DNA but does not affect the nuclear DNA. The performed experiments bring us to the conclusion that the laser irradiation at 1265 nm can affect cells through mitochondrial damage and the inhibition of VDAC enhances effects of PBMT

Peptide Sodium Channels Modulator Mu-Agatoxin-Aa1a Prevents Ischemia-Reperfusion Injury of Cells

Ischemia-reperfusion injury (IRI) is an irreversible functional and structural injury. Restoration of normal oxygen concentration exacerbates the emergence and development of deadly cells. One of the possible moments of reperfusion damage to cells is an increase in the intracellular concentration of sodium ions. In this article, we study the mu-agatoxin-Aa1a, a modulator of sodium channels, on the processes of IRI cells damage. The toxin was synthesized using an automatic peptide synthesizer. Hypoxia was induced by reducing the content of serum and oxygen in the CHO-K1 culture. The influence of the toxin on the level of apoptosis; intracellular concentration of sodium, calcium, and potassium ions; intracellular pH; totality of reactive oxygen species (ROS), nitric oxide (NO), and ATP; and changes in the mitochondrial potential were studied. The experiments performed show that mu-agatoxin-Aa1a effectively prevents IRI of cells. Toxin reduces the level of apoptosis and prevents a decrease in the intracellular concentration of sodium and calcium ions during IRI. Mu-agatoxin-Aa1a contributes to the maintenance of elevated intracellular pH, reduces the intracellular concentration of ROS, and prevents the decrease in intracellular NO concentration and mitochondrial potential under conditions of reoxygenation/reperfusion. An analysis of experimental data shows that the mu-agatoxin-Aa1a peptide has adaptogenic properties. In the future, this peptide can be used to prevent ischemia/reperfusion tissue damage different genesis

Protective Effect of Peptide Calcium Channel Blocker Omega-Hexatoxin-Hv1a on Epithelial Cell during Ischemia–Reperfusion Injury

Ischemia–reperfusion injury (IRI) is a common phenomenon that develops both from natural causes and during major operations. Many intracellular processes mediated by calcium ions are involved in the development of IRI. Currently, chemical calcium channel blockers are used but they have a number of limitations. In this article, we study the effect of the omega-hexatoxin-Hv1a peptide toxin, an alternative to chemical calcium channel blockers, on the mechanisms of IRI development in epithelial cell culture. The toxin was produced using solid phase peptide synthesis. IRI was caused by deprivation of glucose, serum and oxygen. The data obtained demonstrate that the omega-hexatoxin-Hv1a toxin in nanomolar concentrations is able to prevent the development of apoptosis and necrosis in epithelial cells by reducing the concentration of calcium, sodium and potassium ions, as well as by delaying rapid normalization of the pH level, affecting the mitochondrial potential and oxidative stress. This toxin can be used as an alternative to chemical calcium channel blockers for preventing tissue and organ IRI due to its low-dose requirement and high bioavailability