Fully automated synthesis of [<sup>18</sup>F]fluoro‐dihydrotestosterone ([<sup>18</sup>F]FDHT) using the FlexLab module

Ackermann, Uwe; Lewis, Jason S.; Young, Kenneth C.; Morris, Michael J.; Weickhardt, Andrew; Davis, Ian D.; Scott, Andrew M.

doi:10.1002/jlcr.3417

Cited by 12 publications

(8 citation statements)

References 16 publications

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“…[ 18 F]-FDHT was synthesized as previously described 19 with minor modifications, using a Synthra RNplus module (Synthra GMBH, Hamburg, Germany) in a fully automated process with an overall radiosynthesis time of 100 min, the radiochemical yield of 16.43 ± 2.6% (n = 10), decay corrected to the end of the bombardment, and radiochemical purity routinely greater than 99%. Quality control was performed by radio-TLC and analytical reverse-phase HPLC, by using co-elution with a non-radioactive reference standard, FDHT (ABX, Radeberg, Germany).…”

Section: Methodsmentioning

confidence: 99%

[18F]-FDHT PET/CT as a tool for imaging androgen receptor expression in high-grade glioma

Orevi

Shamni

Zalcman

et al. 2021

Neuro-Oncology Advances

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Background Glioblastoma (GBM) is associated with poor overall survival. Recently, we showed that androgen receptor (AR) protein is overexpressed in 56% of GBM specimens and AR antagonists induced dose-dependent death in several GBM cell lines and significantly reduced tumor growth and prolonged the lifespan of mice implanted with human GBM. 16β-18F-fluoro-5α-dihydrotestosterone ([18F]-FDHT) is a PET tracer used to detect AR expression in prostate and breast cancers. This study was aimed at exploring the ability of [18F]-FDHT-PET to detect AR expression in high-grade gliomas. Methods Twelve patients with suspected high-grade glioma underwent a regular workup and additional dynamic and static [ 18 F]-FDHT-PET/CT. Visual and quantitative analyses of [ 18 F]-FDHT kinetics in the tumor and normal brain were performed. Mean and maximum (max) standardized uptake values (SUVs) were determined in selected volumes of interest. The patients had surgery or biopsy after PET/CT. AR protein was analyzed in the tumor samples by western blot. Fold change in AR expression was calculated by densitometry analysis. Correlation between imaging and AR protein samples was determined. Results In six of the 12 patients, [ 18 F]-FDHT uptake was significantly higher in the tumor than in the normal brain. These patients also had increased AR protein expression within the tumor. Pearson correlation coefficient analysis for the tumor-to-control normal brain uptake ratio in terms of SUVmean versus AR protein expression, was positive and significant (R = 0.84; p = 0.002). Conclusion [ 18 F]-FDHT-PET/CT could identify increased AR expression in high-grade glioma.

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Section: Methodsmentioning

confidence: 99%

[18F]-FDHT PET/CT as a tool for imaging androgen receptor expression in high-grade glioma

Orevi

Shamni

Zalcman

et al. 2021

Neuro-Oncology Advances

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“…The next step was to reduce the intermediate 3 . The originally reported literature method used a strong reducing agent, LiAlH 4 which had been successfully replaced by a milder reducing agent, NaBH 4, for better compatibility in the automated module [13,24]. However, it has been mentioned in the literature that the quenching of a large excess of NaBH 4 with acetone is necessary, otherwise, it can further reduce the deprotected ketone produced during the acid deprotection step, resulting in significant decomposition of [ 18 F]FDHT [13].…”

Section: Resultsmentioning

confidence: 99%

“…Later the mild reducing agent, NaBH 4 , was used for better compatibility in an automated synthesis module [13]. Further improvements have been reported using a fully automated radiolabeling procedure [24]. Herein we report the radiosynthesis of [ 18 F]FFNP and [ 18 F]FDHT via the “fluorination on Sep-Pak” strategy.…”

Section: Introductionmentioning

confidence: 99%

Fluorine-18 Labeled Fluorofuranylnorprogesterone ([18F]FFNP) and Dihydrotestosterone ([18F]FDHT) Prepared by “Fluorination on Sep-Pak” Method

et al. 2019

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To further explore the scope of our recently developed “fluorination on Sep-Pak” method, we prepared two well-known positron emission tomography (PET) tracers 21-[18F]fluoro-16α,17α-[(R)-(1′-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione furanyl norprogesterone ([18F]FFNP) and 16β-[18F]fluoro-5α-dihydrotestosterone ([18F]FDHT). Following the “fluorination on Sep-Pak” method, over 70% elution efficiency was observed with 3 mg of triflate precursor of [18F]FFNP. The overall yield of [18F]FFNP was 64–72% (decay corrected) in 40 min synthesis time with a molar activity of 37–81 GBq/µmol (1000–2200 Ci/mmol). Slightly lower elution efficiency (~55%) was observed with the triflate precursor of [18F]FDHT. Fluorine-18 labeling, reduction, and deprotection to prepare [18F]FDHT were performed on Sep-Pak cartridges (PS-HCO3 and Sep-Pak plus C-18). The overall yield of [18F]FDHT was 25–32% (decay corrected) in 70 min. The molar activity determined by using mass spectrometry was 63–148 GBq/µmol (1700–4000 Ci/mmol). Applying this quantitative measure of molar activity to in vitro assays [18F]FDHT exhibited high-affinity binding to androgen receptors (Kd~2.5 nM) providing biological validation of this method.

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“…Additionally, simple operations should be automated to enable the high reproducibility of reagent adjustments, because personal differences in manual dispensing operations can greatly affect the results of the adjustments. Hence, there are some groups that promote mechanical automation [10], but most other groups have difficulty installing expensive, large equipment.…”

Section: Introductionmentioning

confidence: 99%

Electrowetting on Dielectric (EWOD) Device with Dimple Structures for Highly Accurate Droplet Manipulation

et al. 2019

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Digital microfluidics based on electrowetting on dielectric (EWOD) devices has potential as a fundamental technology for the accurate preparation of dangerous reagents, the high-speed dispensing of rapidly deteriorating reagents, and the fine adjustment of expensive reagents, such as the preparation of for positron emission tomography (PET). To allow single substrate type EWODs to be practically used in an automatic operation system, we developed a dimple structure as a key technique for a highly accurate droplet manipulation method. The three-dimensional shape of the dimple structure is embossed onto a disposable thin sheet. In this study, we confirmed that the dimple structure can suppress unintended droplet motion caused by unidentified factors. In addition, the stability of the droplets on the dimple structures was evaluated using a sliding experiment. On a flat substrate, the success rate of a droplet motion was lower than 70.8%, but on the dimple structure, the droplets were able to be moved along the dimple structures correctly without unintended motion caused by several environmental conditions. These results indicated that the dimple structure increased the controllability of the droplets. Hence, the dimple structure will contribute to the practical application of digital microfluidics based on single substrate type EWODs.

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Fully automated synthesis of [¹⁸F]fluoro‐dihydrotestosterone ([¹⁸F]FDHT) using the FlexLab module

Abstract: Graphical abstract

Cited by 12 publications

References 16 publications

[18F]-FDHT PET/CT as a tool for imaging androgen receptor expression in high-grade glioma

[18F]-FDHT PET/CT as a tool for imaging androgen receptor expression in high-grade glioma

Fluorine-18 Labeled Fluorofuranylnorprogesterone ([18F]FFNP) and Dihydrotestosterone ([18F]FDHT) Prepared by “Fluorination on Sep-Pak” Method

Electrowetting on Dielectric (EWOD) Device with Dimple Structures for Highly Accurate Droplet Manipulation

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Fully automated synthesis of [18F]fluoro‐dihydrotestosterone ([18F]FDHT) using the FlexLab module

Abstract: Graphical abstract

Cited by 12 publications

References 16 publications

[18F]-FDHT PET/CT as a tool for imaging androgen receptor expression in high-grade glioma

[18F]-FDHT PET/CT as a tool for imaging androgen receptor expression in high-grade glioma

Fluorine-18 Labeled Fluorofuranylnorprogesterone ([18F]FFNP) and Dihydrotestosterone ([18F]FDHT) Prepared by “Fluorination on Sep-Pak” Method

Electrowetting on Dielectric (EWOD) Device with Dimple Structures for Highly Accurate Droplet Manipulation

Contact Info

Product

Resources

About

Fully automated synthesis of [¹⁸F]fluoro‐dihydrotestosterone ([¹⁸F]FDHT) using the FlexLab module