Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals

Kuntzsch, Matthias; Lamparter, Denis; Brüggener, Nils; Müller, Marco; Kienzle, Gabriele; Reischl, Gerald

doi:10.3390/ph7050621

Cited by 37 publications

(20 citation statements)

References 12 publications

(12 reference statements)

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“…Plot of ionic volume against inhibitory potency (logIC 50 based on ability to block anion uptake in NIS-expressing cells) for univalent anions examined in this work and other published works (5)(6)(7)9,17). Differing methods, cell lines, probes, and counter-ions were used in each study; further details are given in Supplemental (59 6 10 %ID/g), and salivary glands (18 6 4 %ID/g); uptake in these organs was reduced to 4.3 6 4.6, 3.0 6 1.7, and 2.6 6 1.7 % ID/g, respectively, in mice administered NaClO 4 (Fig.…”

Section: Ex Vivo Biodistribution In Micementioning

confidence: 82%

“…The limit of detection was 894 ng/mL for KSO 3 F. Pyridine was determined by high-performance liquid chromatography (1200 series; Agilent), with the ultraviolet/visible detector adjusted to 210 nm, on a Zorbax 300-SCX column (Agilent) eluted with 0.2 M sodium phosphate, pH 3, at 1.0 mL/min. The K[2.2.2] concentration was determined as described previously (17). HCT116-hNIS-C19 cells seeded in 12-well plates (5 · 10 5 cells per well) were incubated with 5% CO 2 at 37°C for 24 h, washed twice with Hanks balanced salt solution (HBSS), and then incubated for 30 min in HBSS with the chosen inhibitory anion (700 mL of a 1 · 10 22 to 1 · 10 213 M concentration, n 5 3 each).…”

Section: Optimized Radiosynthesismentioning

confidence: 99%

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¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

et al. 2016

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Anion transport by the human sodium-iodide symporter (hNIS) is an established target for molecular imaging and radionuclide therapy. Current radiotracers for PET of hNIS expression are limited to 124 I 2 and 18 F-BF 4 2 . We sought new 18 F-labeled hNIS substrates offering higher specific activity, higher affinity, and simpler radiochemical synthesis than 18 F-BF 4 2 . Methods: The ability of a range of anions, some containing fluorine, to block 99m TcO 4 2 uptake in hNIS-expressing cells was measured. SO 3 F 2 emerged as a promising candidate. 18 F-SO 3 F 2 was synthesized by reaction of 18 F 2 with SO 3 -pyridine complex in MeCN and purified using alumina and quaternary methyl ammonium solid-phase extraction cartridges. Chemical and radiochemical purity and serum stability were determined by radiochromatography. Radiotracer uptake and efflux in hNIS-transduced HCT116-C19 cells and the hNIS-negative parent cell line were evaluated in vitro in the presence and absence of a known competitive inhibitor (NaClO 4 ). PET/CT imaging and ex vivo biodistribution measurement were conducted on BALB/c mice, with and without NaClO 4 inhibition. Results: Fluorosulfate was identified as a potent inhibitor of 99m TcO 4 2 uptake via hNIS in vitro (half-maximal inhibitory concentration, 0.55-0.56 mM (in comparison with 0.29-4.5 mM for BF 4 2 , 0.07 mM for TcO 4 2 , and 2.7-4.7 mM for I 2 ). Radiolabeling to produce 18 F-SO 3 F 2 was simple and afforded high radiochemical purity suitable for biologic evaluation (radiochemical purity . 95%, decay-corrected radiochemical yield 5 31.6%, specific activity $ 48.5 GBq/mmol). Specific, blockable hNIS-mediated uptake in HCT116-C19 cells was observed in vitro, and PET/CT imaging of normal mice showed uptake in thyroid, salivary glands (percentage injected dose/g at 30 min, 563 6 140 and 32 6 9, respectively), and stomach (percentage injected dose/g at 90 min, 68 6 21). Conclusion: Fluorosulfate is a high-affinity hNIS substrate. 18 F-SO 3 F 2 is easily synthesized in high yield and very high specific activity and is a promising candidate for preclinical and clinical PET imaging of hNIS expression and thyroid-related disease; it is the first example of in vivo PET imaging with a tracer containing an S-18 F bond.

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Section: Ex Vivo Biodistribution In Micementioning

confidence: 82%

Section: Optimized Radiosynthesismentioning

confidence: 99%

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

et al. 2016

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“…As a result, other phase transfer reagents were tested. The [ 18 F]F‐DA product using TBA HCO 3 consistently contained <50 μg/mL of residual TBA HCO 3 when visually compared with reference standards (n = 8) based on the method of Kuntzsch et al (Figure ). This qualitative, visual test was quick and easy to perform, making it amenable for quality control analysis during production for human use.…”

Section: Resultsmentioning

confidence: 99%

Improved, one‐pot synthesis of 6‐[¹⁸F]fluorodopamine and quality control testing for use in patients with neuroblastoma

Vāvere

Neumann

Butch

et al. 2018

Labelled Comp Radiopharmac

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6‐[18F]Fluorodopamine ([18F]F‐DA) is taken into cells via the norepinephrine transporter (NET). Recent [18F]F‐DA positron emission tomography–computed tomography (PET‐CT) imaging of adult neuroendocrine tumors shows a dramatic improvement in sensitivity over the standard‐of‐care, meta‐iodobenzylguanidine (MIBG) single‐photon emission computed tomography (SPECT)–CT. A new precursor (ALPdopamine™) allows no‐carrier‐added synthesis resulting in high–molar activity [18F]F‐DA. Automated synthesis of [18F]F‐DA was performed in a single reactor using a two‐step procedure: 1) fluorination via thermolysis of a diaryliodonium salt precursor, followed by 2) acid hydrolysis. Phase transfer agents, Kryptofix 222 and two tetraalkylammonium salts, were investigated. Optimized synthesis of [18F]F‐DA was achieved in 56 to 60 minutes (26% end of synthesis [EOS], nondecay corrected). The product passed all Food and Drug Administration (FDA)–required quality control testing for human use. Accumulation of [18F]F‐DA in SK‐N‐BE(2)‐C (high NET expression) cells was significantly higher than in SH‐EP (minimal NET expression) cells (P < 0.0001). ALPdopamine provides an effective scaffold for the routine production of [18F]F‐DA for human use. Validation of uptake by neuroblastoma (NB) cell lines supports the use of [18F]F‐DA for imaging NB patients. A pediatric NB imaging trial using [18F]F‐DA PET has been approved (Investigational New Drug application (IND) no. 138638) based on the methods reported here. We expect [18F]F‐DA will be localized in NB tumors and that high‐quality functional images will be obtained within minutes after injection.

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“…For residual tetrabutylammonium ion (TBA), the TLC spot test from Kuntzsch et al [29] was used with slight modifications. TLC was performed using Polygram SIL G/ UV254 (Macherey-Nagel) 4 x 8 cm.…”

Section: Thin Layer Chromatography (Tlc)mentioning

confidence: 99%

Procedures for the GMP-Compliant Production and Quality Control of [<sup>18</sup>F]PSMA-1007—A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer

Cardinale

Martin

Remde

et al. 2017

Preprint

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Radiolabelled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection we recently developed the fluorine-18 labelled PSMA-ligand [ 18 F]PSMA-1007 as next generation radiofluorinated Glu-ureido PSMA inhibitor after [ 18 F]DCFPyL and [ 18 F]DCFBC. Since radiosynthesis so far was suffering for rather poor yields novel procedures for the automated radiosyntheses of [ 18 F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly used radiosynthesisers. Using the novel one-step procedure the [ 18 F]PSMA-1007 was produced in good radiochemical yields ranging from 30-70 % and synthesis times less than 55 minutes. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and at the same time high yielding production pathway for the next generation PSMA radioligand [ 18 F]PSMA-1007. Actually it turned out that the radiosynthesis is as easily realised as the well-known [ 18 F]FDG synthesis and thus transferable onto all currently available radiosynthesisers. Using the new procedures, clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

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Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals

Cited by 37 publications

References 12 publications

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

Improved, one‐pot synthesis of 6‐[¹⁸F]fluorodopamine and quality control testing for use in patients with neuroblastoma

Procedures for the GMP-Compliant Production and Quality Control of [<sup>18</sup>F]PSMA-1007—A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer

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Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals

Cited by 37 publications

References 12 publications

18F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

18F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

Improved, one‐pot synthesis of 6‐[18F]fluorodopamine and quality control testing for use in patients with neuroblastoma

Procedures for the GMP-Compliant Production and Quality Control of [<sup>18</sup>F]PSMA-1007&mdash;A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer

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Product

Resources

About

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

Improved, one‐pot synthesis of 6‐[¹⁸F]fluorodopamine and quality control testing for use in patients with neuroblastoma

Procedures for the GMP-Compliant Production and Quality Control of [<sup>18</sup>F]PSMA-1007—A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer