scholarly journals 66Ga: A Novelty or a Valuable Preclinical Screening Tool for the Design of Targeted Radiopharmaceuticals?

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2575 ◽  
Author(s):  
Alejandro Amor-Coarasa ◽  
James Kelly ◽  
Shashikanth Ponnala ◽  
Anastasia Nikolopoulou ◽  
Clarence Williams ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Chemical Properties ◽  
Radiochemical Yield ◽  
Anion Exchange Column ◽  
Molar Activity ◽  
Multiple Challenges ◽  
Plasma Half Life ◽  
Preclinical Screening ◽  
And Chemical Properties

Emerging interest in extending the plasma half-life of small molecule radioligands warrants a consideration of the appropriate radionuclide for PET imaging at longer time points (>8 h). Among candidate positron-emitting radionuclides, 66Ga (t1/2 = 9.5 h, β+ = 57%) has suitable nuclear and chemical properties for the labeling and PET imaging of radioligands of this profile. We investigated the value of 66Ga to preclinical screening and the evaluation of albumin-binding PSMA-targeting small molecules. 66Ga was produced by irradiation of a natZn target. 66Ga3+ ions were separated from Zn2+ ions by an optimized UTEVA anion exchange column that retained 99.99987% of Zn2+ ions and allowed 90.2 ± 2.8% recovery of 66Ga3+. Three ligands were radiolabeled in 46.4 ± 20.5%; radiochemical yield and >90% radiochemical purity. Molar activity was 632 ± 380 MBq/µmol. Uptake in the tumor and kidneys at 1, 3, 6, and 24 h p.i. was determined by µPET/CT imaging and more completely predicted the distribution kinetics than uptake of the [68Ga]Ga-labeled ligands did. Although there are multiple challenges to the use of 66Ga for clinical PET imaging, it can be a valuable research tool for ligand screening and preclinical imaging beyond 24 h.

scholarly journals Novel late-stage radiosynthesis of 5-[18F]-trifluoromethyl-1,2,4-oxadiazole (TFMO) containing molecules for PET imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nashaat Turkman ◽  
Daxing Liu ◽  
Isabella Pirola
Keyword(s):  
Late Stage ◽  
Histone Deacetylases ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Single Step ◽  
The Novel ◽  
Molar Activity ◽  
The Central Nervous System ◽  
Class Iia Hdacs ◽  
18F Fluoride

AbstractSmall molecules that contain the (TFMO) moiety were reported to specifically inhibit the class-IIa histone deacetylases (HDACs), an important target in cancer and the disorders of the central nervous system (CNS). However, radiolabeling methods to incorporate the [18F]fluoride into the TFMO moiety are lacking. Herein, we report a novel late-stage incorporation of [18F]fluoride into the TFMO moiety in a single radiochemical step. In this approach the bromodifluoromethyl-1,2,4-oxadiazole was converted into [18F]TFMO via no-carrier-added bromine-[18F]fluoride exchange in a single step, thus producing the PET tracers with acceptable radiochemical yield (3–5%), high radiochemical purity (> 98%) and moderate molar activity of 0.33–0.49 GBq/umol (8.9–13.4 mCi/umol). We validated the utility of the novel radiochemical design by the radiosynthesis of [18F]TMP195, which is a known TFMO containing potent inhibitor of class-IIa HDACs.

scholarly journals 2-Nitroimidazole-Furanoside Derivatives for Hypoxia Imaging—Investigation of Nucleoside Transporter Interaction, 18F-Labeling and Preclinical PET Imaging

2019 ◽  
Vol 12 (1) ◽  
pp. 31
Author(s):  
Florian Maier ◽  
Anna Schweifer ◽  
Vijaya Damaraju ◽  
Carol Cass ◽  
Gregory Bowden ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Tumor Hypoxia ◽  
Radiochemical Yield ◽  
Nucleoside Transporters ◽  
Nucleoside Transporter ◽  
Hypoxia Imaging ◽  
Molar Activity ◽  
Slow Kinetics ◽  
Sugar Derivatives

The benefits of PET imaging of tumor hypoxia in patient management has been demonstrated in many examples and with various tracers over the last years. Although, the optimal hypoxia imaging agent has yet to be found, 2-nitroimidazole (azomycin) sugar derivatives—mimicking nucleosides—have proven their potential with [18F]FAZA ([18F]fluoro-azomycin-α-arabinoside) as a prominent representative in clinical use. Still, for all of these tracers, cellular uptake by passive diffusion is postulated with the disadvantage of slow kinetics and low tumor-to-background ratios. We recently evaluated [18F]fluoro-azomycin-β-deoxyriboside (β-[18F]FAZDR), with a structure more similar to nucleosides than [18F]FAZA and possible interaction with nucleoside transporters. For a deeper insight, we comparatively studied the interaction of FAZA, β-FAZA, α-FAZDR and β-FAZDR with nucleoside transporters (SLC29A1/2 and SLC28A1/2/3) in vitro, showing variable interactions of the compounds. The highest interactions being for β-FAZDR (IC50 124 ± 33 µM for SLC28A3), but also for FAZA with the non-nucleosidic α-configuration, the interactions were remarkable (290 ± 44 µM {SLC28A1}; 640 ± 10 µM {SLC28A2}). An improved synthesis was developed for β-FAZA. For a PET study in tumor-bearing mice, α-[18F]FAZDR was synthesized (radiochemical yield: 15.9 ± 9.0% (n = 3), max. 10.3 GBq, molar activity > 50 GBq/µmol) and compared to β-[18F]FAZDR and [18F]FMISO, the hypoxia imaging gold standard. We observed highest tumor-to-muscle ratios (TMR) for β-[18F]FAZDR already at 1 h p.i. (2.52 ± 0.94, n = 4) in comparison to [18F]FMISO (1.37 ± 0.11, n = 5) and α-[18F]FAZDR (1.93 ± 0.39, n = 4), with possible mediation by the involvement of nucleoside transporters. After 3 h p.i., TMR were not significantly different for all 3 tracers (2.5–3.0). Highest clearance from tumor tissue was observed for β-[18F]FAZDR (56.6 ± 6.8%, 2 h p.i.), followed by α-[18F]FAZDR (34.2 ± 7.5%) and [18F]FMISO (11.8 ± 6.5%). In conclusion, both isomers of [18F]FAZDR showed their potential as PET hypoxia tracers. Differences in uptake behavior may be attributed to a potential variable involvement of transport mechanisms.

scholarly journals Synthesis of a novel 89Zr labeled HER2 affibody and its application study in tumor PET imaging

2020 ◽  
Author(s):  
Yuping Xu ◽  
Lizhen Wang ◽  
Donghui Pan ◽  
Junjie Yan ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Ex Vivo ◽  
Radiochemical Yield ◽  
Immunohistochemical Analysis ◽  
In Vivo Studies ◽  
Potential Candidate ◽  
Synthesis Time ◽  
Normal Tissues

Abstract Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89Zr-labeled HER2 affibody, [89Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [89Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2±1.9% , and the radiochemical purity was higher than 95%. The total synthesis time was only 30 minutes. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5%IA/g during 48 hours postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels（~1%IA/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [89Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.

scholarly journals Synthesis of a novel 89Zr labeled HER2 affibody and its application study in tumor PET imaging

2020 ◽  
Author(s):  
Yuping Xu ◽  
Lizhen Wang ◽  
Donghui Pan ◽  
Junjie Yan ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Ex Vivo ◽  
Radiochemical Yield ◽  
Immunohistochemical Analysis ◽  
In Vivo Studies ◽  
Potential Candidate ◽  
Synthesis Time ◽  
Normal Tissues

Abstract Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89 Zr-labeled HER2 affibody, [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [ 89 Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2±1.9% , and the radiochemical purity was higher than 95%. The total synthesis time was only 30 minutes. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5%IA/g during 48 hours postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels（~1%IA/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.

scholarly journals Microfluidic Radiosynthesis of the Muscarinic M2 Imaging Agent [18F]FP-TZTP

2018 ◽  
Vol 71 (10) ◽  
pp. 811 ◽  
Author(s):  
Lidia Matesic ◽  
Ivan Greguric ◽  
Giancarlo Pascali
Keyword(s):  
Radiochemical Purity ◽  
Muscarinic Acetylcholine Receptor ◽  
Reaction Times ◽  
Radiochemical Yield ◽  
Receptor Subtype ◽  
Chemical Reagents ◽  
Molar Activity ◽  
Positron Emission ◽  
Radiochemical Yields ◽  
Pet Scans

3-(4-(3-[18F]Fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5,6-tetrahydropyridine ([18F]FP-TZTP) is a selective 18F-radiotracer for the muscarinic acetylcholine receptor subtype M2, which can be used to perform positron emission tomography (PET) scans on patients with neurological disorders such as Alzheimer’s disease. [18F]FP-TZTP was produced using continuous-flow microfluidics, a technique that uses reduced amounts of chemical reagents, shorter reaction times and in general, results in higher radiochemical yields compared to currently used techniques. The optimal 18F-radiolabelling conditions consisted of a total flow rate of 40 µL min−1 and 190°C, which produced [18F]FP-TZTP in 26 ± 10 % radiochemical yield with a molar activity of 182 ± 65 GBq µmol−1 and >99 % radiochemical purity.

The Synthesis and Chemical Properties of 3-Chloromercury-2-Hydroxipropyl-Urea

1975 ◽  
Vol 14 (04) ◽  
pp. 374-380
Author(s):  
I. Berkeš ◽  
V. Jovanović ◽  
D. Živanov-Stakić
Keyword(s):  
Rapid Method ◽  
Room Temperature ◽  
Chromatographic Method ◽  
Radiochemical Purity ◽  
Inorganic Mercury ◽  
Chemical Properties ◽  
Thermal Sterilization ◽  
Human Use ◽  
And Chemical Properties

SummaryA simple and rapid method for the synthesis of 3-chloromercury-2-hydroxipropyl-urea has been described. It has been concluded that highest yields are obtained by the synthesis of 197HgO and allyl urea in the ratio of 2.5: 1.Stability of the final preparation was investigated after thermal sterilization and standing at room temperature. It has been proved that the inorganic mercury-197 is not released. Radiochemical purity was controlled by chromatographic method using pyridine, n-butanol and water (3: 10: 3 v/v) as a solvent. The results obtained indicate that the preparation is applicable for human use.

scholarly journals Synthesis and Initial In Vivo Evaluation of [11C]AZ683—A Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R)

2018 ◽  
Vol 11 (4) ◽  
pp. 136 ◽  
Author(s):  
Sean Tanzey ◽  
Xia Shao ◽  
Jenelle Stauff ◽  
Janna Arteaga ◽  
Phillip Sherman ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Colony Stimulating Factor ◽  
In Vivo Evaluation ◽  
Molar Activity ◽  
Positron Emission ◽  
New Strategy ◽  
Activity Yield ◽  
Stimulating Factor

Positron emission tomography (PET) imaging of Colony Stimulating Factor 1 Receptor (CSF1R) is a new strategy for quantifying both neuroinflammation and inflammation in the periphery since CSF1R is expressed on microglia and macrophages. AZ683 has high affinity for CSF1R (Ki = 8 nM; IC50 = 6 nM) and >250-fold selectivity over 95 other kinases. In this paper, we report the radiosynthesis of [11C]AZ683 and initial evaluation of its use in CSF1R PET. [11C]AZ683 was synthesized by 11C-methylation of the desmethyl precursor with [11C]MeOTf in 3.0% non-corrected activity yield (based upon [11C]MeOTf), >99% radiochemical purity and high molar activity. Preliminary PET imaging with [11C]AZ683 revealed low brain uptake in rodents and nonhuman primates, suggesting that imaging neuroinflammation could be challenging but that the radiopharmaceutical could still be useful for peripheral imaging of inflammation.

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

2021 ◽  
Author(s):  
Richard Edwards ◽  
Hannah E. Greenwood ◽  
Graeme McRobbie ◽  
Imtiaz Khan ◽  
Timothy H. Witney
Keyword(s):  
Large Scale ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Automated Synthesis ◽  
Molar Activity ◽  
Positron Emission ◽  
Optimized Protocol ◽  
Cancer Types ◽  
Automated Procedures ◽  
Phosphate Buffered Saline

Abstract Purpose (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 xC-, 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. Procedures An automated synthesis and purification of [18F]FSPG was developed using 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 radio-HPLC. Purification of [18F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, 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. Results The optimized protocol produced [18F]FSPG in 38.4 ± 2.6 % radiochemical yield and >96 % radiochemical purity with a molar activity of 11.1 ± 7.7 GBq/μmol. Small alterations, including the implementation of a reverse elution and an altered Hypercarb cartridge, led 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. Conclusions We have developed a robust and facile method for [18F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. 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 a cassette-based radiosynthesis on an automated synthesis module routinely used for clinical production makes the method amenable to rapid and widespread clinical translation.

scholarly journals Zirconium-89 Labeled Antibodies: A New Tool for Molecular Imaging in Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Floor C. J. van de Watering ◽  
Mark Rijpkema ◽  
Lars Perk ◽  
Ulrich Brinkmann ◽  
Wim J. G. Oyen ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Clinical Studies ◽  
Chemical Properties ◽  
Imaging Method ◽  
Positron Emission ◽  
Valuable Method ◽  
Ongoing Development ◽  
The Individual ◽  
Physical And Chemical ◽  
And Chemical Properties

Antibody based positron emission tomography (immuno-PET) imaging is of increasing importance to visualize and characterize tumor lesions. Additionally, it can be used to identify patients who may benefit from a particular therapy and monitor the therapy outcome. In recent years the field is focused on89Zr, a radiometal with near ideal physical and chemical properties for immuno-PET. In this review we will discuss the production of  89Zr, the bioconjugation strategies, and applications in (pre-)clinical studies of  89Zr-based immuno-PET in oncology. To date,89Zr-based PET imaging has been investigated in a wide variety of cancer-related targets. Moreover, clinical studies have shown the feasibility for89Zr-based immuno-PET to predict and monitor treatment, which could be used to tailor treatment for the individual patient. Further research should be directed towards the development of standardized and robust conjugation methods and improved chelators to minimize the amount of released Zr4+from the antibodies. Additionally, further validation of the imaging method is required. The ongoing development of new89Zr-labeled antibodies directed against novel tumor targets is expected to expand applications of  89Zr-labeled immuno-PET to a valuable method in the medical imaging.

Statistical criteria of stellar population types

1966 ◽  
Vol 24 ◽  
pp. 101-110
Author(s):  
W. Iwanowska
Keyword(s):  
Stellar Population ◽  
Chemical Properties ◽  
Spectrophotometric Study ◽  
Physical And Chemical Properties ◽  
Population Type ◽  
The Galaxy ◽  
Distribution Parameters ◽  
Physical And Chemical ◽  
Statistical Criteria ◽  
And Chemical Properties

In connection with the spectrophotometric study of population-type characteristics of various kinds of stars, a statistical analysis of kinematical and distribution parameters of the same stars is performed at the Toruń Observatory. This has a twofold purpose: first, to provide a practical guide in selecting stars for observing programmes, second, to contribute to the understanding of relations existing between the physical and chemical properties of stars and their kinematics and distribution in the Galaxy.

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