Synthesis of 18F-labelled 2-fluoroethyl-nitrosoureas

1984 ◽  
Vol 62 (11) ◽  
pp. 2107-2112 ◽  
Author(s):  
Simin Farrokhzad ◽  
Mirko Diksic ◽  
Lucas Y. Yamamoto ◽  
William Feindel
Keyword(s):  
Radiochemical Purity ◽  
Specific Activity ◽  
Radiochemical Yield ◽  
Nucleophilic Attack ◽  
Aziridine Ring ◽  
Geometrical Isomers ◽  
Isomeric Mixture

18F-labelled 1,3-bis-(2-fluoroethyl) nitrosourea (18F-BFNU) (9) and 1-(2-chloroethyl)-3-(2-fluoroethyl) nitrosourea (18F-CFNU) (isomeric mixture, 11,12) were synthesized by nucleophilic attack of 18F-labelled tetra-n-butylammonium fluoride on the aziridine ring of 1,3-substituted ureas. Diethyleneurea (DEU) (5), 1-(2-fluoroethyl)-3-ethyleneurea (FEU) (7), and 1-(2-chloroethyl)-3-ethyleneurea (CEU) (14) were used as starting materials in the synthesis. Nitrosation of 18F-labelled 1,3-bis-(2-fluoroethyl) urea (18F-BFU) (6) produced 18F-BFNU with a radiochemical yield of 5–10%. Nitrosation of 18F-labelled 1-(2-chloroethyl)-3-(2-fluoroethyl) urea (18F-CFU) (15) gave 18F-CFNU as a mixture of two isomers. Geometrical isomers of CFNU were separated by hplc, and the radiochemical yield of the two isomers ranged from 8% to 15%, with a radiochemical purity exceeding 96%. Syntheses, which took about 60 min, yielded products with specific activity of 680 mCi/mmol when n-Bu4N+F− was used, or 300 mCi/mmol when HF was used to complete the opening of the aziridine ring.

Radiosynthesis of a Novel PET Fluoronicotinamide for Melanoma Tumour PET Imaging; [18F]MEL050

2011 ◽  
Vol 64 (7) ◽  
pp. 873 ◽  
Author(s):  
Ivan Greguric ◽  
Stephen Taylor ◽  
Tien Pham ◽  
Naomi Wyatt ◽  
Cathy D. Jiang ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Large Scale ◽  
Radiochemical Purity ◽  
Specific Activity ◽  
Phase 1 ◽  
Radiochemical Yield ◽  
Synthesis Time ◽  
Clinical Phase ◽  
One Step ◽  
No Carrier Added

[18F]6-Fluoro-N-[2-(diethylamino)ethyl]nicotinamide [18F]MEL050 is a novel nicotinamide-based radiotracer, designed to target random metastatic dissemination of melanoma tumours by targeting melanin. Preclinical studies suggest that [18F]MEL050 has an excellent potential to improve diagnosis and staging of melanoma. Here we report the radiochemical optimization conditions of [18F]MEL050 and its large scale automated synthesis using a GE FXFN automated radiosynthesis module for clinical, phase-1 investigation. [18F]MEL050 was prepared via a one-step synthesis using no-carrier added K[18F]F-Krytpofix® 222 (DMSO, 170°C, 5 min) followed by HPLC purification. Using 6-chloro-N-[2-(diethylamino)ethyl]nicotinamide as precursor, [18F]MEL050 was obtained in 40–46% radiochemical yield (non-decay corrected), in greater than 99.9% radiochemical purity and specific activity ranging from 240 to 325 GBq μmol–1. Total synthesis time including formulation was 40 min and [18F]MEL050 was stable (99.8%) in PBS for 6 h.

scholarly journals [18F]F-PSMA-1007 Radiolabelling without an On-Site Cyclotron: A Quality Issue

2021 ◽  
Vol 14 (7) ◽  
pp. 599
Author(s):  
Valentina Di Iorio ◽  
Stefano Boschi ◽  
Anna Sarnelli ◽  
Cristina Cuni ◽  
David Bianchini ◽  
...  
Keyword(s):  
Quality Assurance ◽  
Radiochemical Purity ◽  
Competent Authority ◽  
Radiochemical Yield ◽  
Synthesis Process ◽  
Control Parameters ◽  
Quality Issue ◽  
Assurance System ◽  
Quality Control Parameters ◽  
Specific Membrane

Radiopharmaceuticals targeting the prostate-specific membrane antigen (PSMA) has become the gold standard for PET imaging of prostate cancer. [68Ga]Ga-PSMA-11 has been the forerunner but a [18F]F-PSMA ligand has been developed because of the intrinsic advantages of Fluorine-18. Fluorine-18 labelled compounds are usually prepared in centers with an on-site cyclotron. Since our center has not an on-site cyclotron, we decided to verify the feasibility of producing the experimental 18F-labelled radiopharmaceutical [18F]F-PSMA-1007 with [18F]F- from different external suppliers. A quality agreement has been signed with two different suppliers, and a well-established and correctly implemented quality assurance protocol has been followed. The [18F]F- was produced with cyclotrons, on Nb target, but with different beam energy and current. Extensive validation of the [18F]F-PSMA-1007 synthesis process has been performed. The aim of this paper was the description of all the quality documentation which allowed the submission and approval of the Investigational Medicinal Product Dossier (IMPD) to the Competent Authority, addressing the quality problems due to different external suppliers. The result indicates that no significant differences have been found between the [18F]F- from the two suppliers in terms of radionuclidic and radiochemical purity and [18F]F- impacted neither the radiochemical yield of the labelling reaction nor the quality control parameters of the IMP [18F]F-PSMA-1007. These results prove how a correct quality assurance system can overcome some Regulatory Authorities issue that may represent an obstacle to the clinical use of F-18-labelled radiopharmaceuticals without an on-site cyclotron

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 Influence of the Generator in-Growth Time on the Final Radiochemical Purity and Stability of Radiopharmaceuticals

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
L. Uccelli ◽  
A. Boschi ◽  
M. Pasquali ◽  
A. Duatti ◽  
G. Di Domenico ◽  
...  
Keyword(s):  
Nuclear Physics ◽  
Radiochemical Purity ◽  
Specific Activity ◽  
Growth Time ◽  
Direct Production ◽  
Theoretical Investigations ◽  
Standard Quality ◽  
Control Procedures ◽  
Italian National Institute ◽  
Preliminary Irradiation

At Legnaro laboratories of the Italian National Institute for Nuclear Physics (INFN), a feasibility study has started since 2011 related to accelerated-based direct production of by the100Mo(p,2n) reaction. Both theoretical investigations and some recent preliminary irradiation tests on100Mo-enriched samples have pointed out that both the / ratio and the specific activity will be basically different in the final accelerator-produced Tc with respect to generator-produced one, which might affect the radiopharmaceutical procedures. The aim of this work was to evaluate the possible impact of different / isomeric ratios on the preparation of different Tc-labeled pharmaceutical kits. A set of measurements with , eluted from a standard99Mo/ generator, was performed, and results on both radiochemical purity and stability studies (following the standard quality control procedures) are reported for a set of widely used pharmaceuticals (i.e., -Sestamibi, -ECD, -MAG3, -DTPA, -MDP, -HMDP, -nanocolloids, and -DMSA). These pharmaceuticals have been all reconstituted with either the first [O4]−eluate obtained from a99Mo/ generator (coming from two different companies) or eluates after 24, 36, 48, and 72 hours from last elution. Results show that the radiochemical purity and stability of these radiopharmaceuticals were not affected up to the value of 11.84 for the / ratio.

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

2020 ◽  
Author(s):  
Richard Edwards ◽  
Hannah Greenwood ◽  
Timothy Witney
Keyword(s):  
Large Scale ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Reaction Conditions ◽  
Positron Emission ◽  
Optimized Protocol ◽  
Cancer Types ◽  
Automated Procedures ◽  
Phosphate Buffered Saline ◽  
High Radioactivity

<p><i>Purpose</i>: (S)-4-(3-<sup>18</sup>F-Fluoropropyl)-ʟ-Glutamic Acid ([<sup>18</sup>F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x<sub>C</sub><sup>-</sup>, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [<sup>18</sup>F]FSPG production are required. Here, we report a cassette-based method to produce [<sup>18</sup>F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [<sup>18</sup>F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [<sup>18</sup>F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [<sup>18</sup>F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [<sup>18</sup>F]FSPG in phosphate-buffered saline. Subsequently, the [<sup>18</sup>F]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 [<sup>18</sup>F]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 [<sup>18</sup>F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [<sup>18</sup>F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [<sup>18</sup>F]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>

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

2020 ◽  
Author(s):  
Richard Edwards ◽  
Hannah Greenwood ◽  
Timothy Witney
Keyword(s):  
Large Scale ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Reaction Conditions ◽  
Positron Emission ◽  
Optimized Protocol ◽  
Cancer Types ◽  
Automated Procedures ◽  
Phosphate Buffered Saline ◽  
High Radioactivity

<p><i>Purpose</i>: (S)-4-(3-<sup>18</sup>F-Fluoropropyl)-ʟ-Glutamic Acid ([<sup>18</sup>F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system x<sub>C</sub><sup>-</sup>, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [<sup>18</sup>F]FSPG production are required. Here, we report a cassette-based method to produce [<sup>18</sup>F]FSPG at high radioactivity concentrations from low amounts of starting activity.</p><p><i>Procedures</i>: An automated synthesis and purification of [<sup>18</sup>F]FSPG was developed for the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [<sup>18</sup>F]FSPG and by assessing radiochemical purity using radioHPLC. Purification of [<sup>18</sup>F]FSPG was conducted by trapping and washing of the radiotracer on MCX SepPak catridges, followed by a reverse elution of [<sup>18</sup>F]FSPG in phosphate-buffered saline. Subsequently, the [<sup>18</sup>F]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 [<sup>18</sup>F]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 [<sup>18</sup>F]fluoride.</p><p><i>Conclusions: </i>We have developed a robust and facile method for [<sup>18</sup>F]FSPG radiosynthesis in high radiotracer concentration, RCP and RCY. This cassette-based method enabled the production of [<sup>18</sup>F]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>

Self-radiation induced exchange between tritiated water and organic compounds. The labelling of L-chiro-inositol, myo-inositol and Hexa-O-methyl-L-chiro-inositol

1975 ◽  
Vol 28 (9) ◽  
pp. 1981 ◽  
Author(s):  
DHT Fong ◽  
CL Bodkin ◽  
MA Long ◽  
JL Garnett
Keyword(s):  
Organic Compounds ◽  
Radiochemical Purity ◽  
Specific Activity ◽  
Tritiated Water ◽  
High Specific Activity ◽  
Methyl Derivative ◽  
Radiation Induced ◽  
By Products ◽  
Gas Exposure

The stereochemistry of the tritiation of L-chiro-inositol, myo-inositol and hexa-O-methyl-L-chiro-inositol by self-radiation induced exchange with tritiated water of high specific activity has been investigated. Predominance of configurational retention was found to accompany tritium labelling in the two inositols, while substantial configurational inversion occurred in the hexa-O-methyl derivative. Tritiation occurred predominantly at C 1 in L-chiro-inositol, with slight inversion at this position alone accompanying the labelling. Comparison with Wilzbach T2 gas exposure results indicates the HTO method yields less by-products, myo-inositol having a radiochemical purity of 97%.

Fully-Automated Synthesis of 177Lu Labelled FAPI Derivatives On The Module Modular Lab-Eazy

2021 ◽  
Author(s):  
Kurtulus Eryilmaz ◽  
Benan KILBAS
Keyword(s):  
Quality Control ◽  
Chromatographic Analysis ◽  
Radiochemical Purity ◽  
Radiochemical Yield ◽  
Automated System ◽  
Automated Synthesis ◽  
Modular Approach ◽  
Stability Studies ◽  
European Pharmacopoeia ◽  
First Time

Abstract Backround: To the best of our knowledge, manually production of [177Lu]Lu-FAPI radiopharmaceutical derivatives has been only described in literature. In this work, a fully-automated [177Lu]Lu-FAPI synthesis has been well designed for the first time using commercially available synthesis module. In addition to the development of an automated system with disposable cassette, quality control (QC) and stability studies were comprehensively employed. Results A fully automated synthesis of [177Lu]Lu-FAPI derivatives was achieved on the Modular Lab Eazy (ML Eazy) with high radiochemical yield (85–90%). Chromatographic analysis indicated the formation of radiosynthesis with an absolute radiochemical purity (99%). Stability experiments clarified the durability of the products within 4 days. All obtained specifications are consistent to European Pharmacopoeia. Conclusion A fully automated synthesis of [177Lu]Lu-FAPI radiopharmaceuticals were accomplished regarding quality control standards and quality assurance by using commercially available a modular approach namely ML Eazy with disposable customized cassette and template.

scholarly journals F-18 Labeled Vasoactive Intestinal Peptide Analogue in the PET Imaging of Colon Carcinoma in Nude Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Dengfeng Cheng ◽  
Yuxia Liu ◽  
Hua Shen ◽  
Lifang Pang ◽  
Duanzhi Yin ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Colon Carcinoma ◽  
Pet Imaging ◽  
Specific Activity ◽  
Imaging Study ◽  
Radiochemical Yield ◽  
Receptor Imaging ◽  
Improved Stability ◽  
Vip Receptor

As large amount of vasoactive intestinal peptide (VIP) receptors are expressed in various tumors and VIP-related diseases, radiolabeled VIP provides a potential PET imaging agent for VIP receptor. However, structural modification of VIP is required before being radiolabeled and used for VIP receptor imaging due to its poor in vivo stability. As a VIP analogue, [R8, 15, 21, L17]-VIP exhibited improved stability and receptor specificity in preliminary studies. In this study, F-18 labeled [R8,15,21, L17]-VIP was produced with the radiochemical yield being as high as33.6%±3%(decay-for-corrected,n=5) achieved within 100 min, a specific activity of 255 GBq/μmol, and a radiochemical purity as high as 99% as characterized by radioactive HPLC, TLC, and SDS-Page radioautography. A biodistribution study in normal mice also demonstrated fast elimination of F-18 labeled [R8,15,21, L17]-VIP in the blood, liver, and gastrointestinal tracts. A further micro-PET imaging study in C26 colon carcinoma bearing mice confirmed the high tumor specificity, with the tumor/muscle radioactivity uptake ratio being as high as 3.03 at 60 min following injection, and no apparent radioactivity concentration in the intestinal tracts. In addition, blocking experiment and Western Blot test further confirmed its potential in PET imaging of VIP receptor-positive tumor.

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