Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

<p><i>Purpose</i>: (S)-4-(3-¹⁸F-Fluoropropyl)-ʟ-Glutamic Acid ([¹⁸F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x_C^-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [¹⁸F]FSPG production are required. Here, we report a cassette-based method to produce [¹⁸F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [¹⁸F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [¹⁸F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [¹⁸F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [¹⁸F]FSPG in phosphate-buffered saline. Subsequently, the [¹⁸F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.</p><p><i>Results</i>: The optimized protocol produced [¹⁸F]FSPG in 38.4 ± 2.6% RCY and 96% radiochemical purity. Small alterations, including the implementation of a reverse elution and an altered hypercarb cartridge, lead to significant improvements in radiotracer concentration from <10 MBq/mL to >100 MBq/mL. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [¹⁸F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [¹⁸F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [¹⁸F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of cassettes for an ‘out the box’ synthesis on a synthesis module routinely used for clinical production make the method amenable to rapid and widespread clinical translation.</p>

Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

<p><i>Purpose</i>: (S)-4-(3-¹⁸F-Fluoropropyl)-ʟ-Glutamic Acid ([¹⁸F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x_C^-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [¹⁸F]FSPG production are required. Here, we report a cassette-based method to produce [¹⁸F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [¹⁸F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [¹⁸F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [¹⁸F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [¹⁸F]FSPG in phosphate-buffered saline. Subsequently, the [¹⁸F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.</p><p><i>Results</i>: The optimized protocol produced [¹⁸F]FSPG in 38.4 ± 2.6% RCY and 96% radiochemical purity. Small alterations, including the implementation of a reverse elution and an altered hypercarb cartridge, lead to significant improvements in radiotracer concentration from <10 MBq/mL to >100 MBq/mL. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [¹⁸F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [¹⁸F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [¹⁸F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of cassettes for an ‘out the box’ synthesis on a synthesis module routinely used for clinical production make the method amenable to rapid and widespread clinical translation.</p>

Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

<p><i>Purpose</i>: (S)-4-(3-¹⁸F-Fluoropropyl)-ʟ-Glutamic Acid ([¹⁸F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x_C^-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [¹⁸F]FSPG production are required. Here, we report a cassette-based method to produce [¹⁸F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [¹⁸F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [¹⁸F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [¹⁸F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [¹⁸F]FSPG in phosphate-buffered saline. Subsequently, the [¹⁸F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer.</p><p><i>Results</i>: The optimized protocol produced [¹⁸F]FSPG in 38.4 ± 2.6% RCY and 96% radiochemical purity. Small alterations, including the implementation of a reverse elution and an altered hypercarb cartridge, lead to significant improvements in radiotracer concentration from <10 MBq/mL to >100 MBq/mL. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [¹⁸F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [¹⁸F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [¹⁸F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of cassettes for an ‘out the box’ synthesis on a synthesis module routinely used for clinical production make the method amenable to rapid and widespread clinical translation.</p>

Petrogeochemical characteristics and U-Pb age of morion-granite rocks in Central Transbaikalia: Classification and genesis problems

Research subject. This article presents data on the age, material composition, petrogenetical and geochemical properties of morion-containing granites in the Etytei and Khamnigadai massifs of Central Transbaikalia.Materials and methods. The composition of rock samples was investigated using the methods of chemical analysis, XRD and ICP-MS; the age was determined by the zircon U–Pb method using SHRIMP and LA-ICP-MS; the mineral composition was studied using an LEO-1430 electron microscope.Results. The massifs composed of morion-containing granites belong to Early Jurassic (190–185 Ma) and form the peripheral area of the Early Mesozoic Khentei-Dauria magmatic region.Conclusion. According to their petrochemical and mineralogical characteristics, the morion-containing granites under study differ from typical intra-plate granitoids and correspond to the “oxidized” A-type granites. The black smoky colour of quartz contained in granite samples is associated with a relatively high radioactivity of rocks caused by the presence of accessory thorium and uranium-containing minerals.

The main issues of quality assurance of radiopharmaceuticals

One of the prerequisites for successful application of nuclear medicine technologies is the production and clinical use of radiopharmaceuticals (RPs) of a reliably high quality. The aim of the review is to discuss specific properties of RPs, which stipulate specific approaches to their production (or preparation) and quality control. The decisive requirement for the management of RPs at all stages of their life cycle is the observance of the radiation safety rules and regulations. The paper considers the main approaches to assessing the risks of medical radiation exposure to patients and radiation protection of nuclear medicine staff. The choice of a particular quality parameter and the corresponding analytical procedure should be made taking into account the duration of the test, which, like the production time, should be comparable with the radionuclide half-life. The feasibility of the analytical procedure should also be taken into account, given the high radioactivity of the samples tested. Now that theranostics has caught on, new approaches are being developed all over the world concerning regulatory aspects of transition from preclinical studies of RPs to clinical trials, because, according to experts, this is becoming a key condition for rapid implementation of nuclear medicine achievements. The results and conclusions of the present study can be used in the development and expert review of monographs and other specifications required for RP marketing and use. The results of the analysis suggest that it is necessary to develop specific requirements and guidelines for RP testing and evaluation for their successful promotion on the EAEU market.

New measurement of the 241Am(n,2n)240Am cross section

Cross section for 241Am(n,2n)240Am reaction has been measured at the VdG Tandem accelerator of NCSR “Demokritos", at neutron beam energy 10.4 MeV, using the activation technique. The high purity and high radioactivity (5GBq) Am target has been constructed at IRMM, Belgium and consisted of 40 mg Am in the form of AmO2 pressed into pellet with Al2O3 and encapsulated into Al container. The absolute flux of the beam was obtained with respect to the 27Al(n,α)24Na reference reaction. The induced gamma-ray activity of 240Am and 24Na was measured with high resolution HPGe detectors.

Measurement of the 241Am(n,2n)240Am cross section at 17.5 MeV

The 241Am(n,2n)240Am reaction cross section has been measured at neutron beam energy 17.5 MeV, relative to the 27Al(n,α)24Na, 197Au(n,2n)196Au and 93Nb(n,2n)92mNb reference reaction cross sections, using the activation technique. The irradiation was carried out at the Van der Graaff 5.5 MV Tandem accelerator laboratory of NCSR “Demokritos” with monoenergetic neutron beam provided by means of the 3H(d,n)4He reaction, implementing a new Ti-tritiated target. The high purity Am target has been constructed at IRMM, Geel, Belgium and consisted of 40 mg 241Am in the form of AmO2 pressed into pellet with Al2O3 and encapsulated into Al container. Due to this high radioactivity (5 GBq), the Am target was enclosed in a Pb container for safety reasons. After the end of the irradiation, the activity induced by the neutron beam at the target and reference foils, was measured off-line by two 100%, a 50% and a 16% relative efficiency, HPGe detectors.