Optimization of the preparation of fluorine‐18‐labeled steroid receptor ligands 16alpha‐[18F]fluoroestradiol (FES), [18F]fluoro furanyl norprogesterone (FFNP), and 16beta‐[18F]fluoro‐5alpha‐dihydrotestosterone (FDHT) as radiopharmaceuticals

Zhou, Dong; Lin, Min; Yasui, Norio; Al‐Qahtani, Mohammed; Dence, Carmen S.; Schwarz, Sally W.; Katzenellenbogen, John A.

doi:10.1002/jlcr.3191

Cited by 34 publications

(33 citation statements)

References 29 publications

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“…Alterations to the synthesis protocol have been presented as conference abstracts in which, for example, reverse-phase HPLC purification was implemented to allow for rapid and straightforward reformulation using C18 solid-phase extraction after purification (Nickels et al, 2014). In addition, the use of NaBH 4 as a milder reducing agent was recently optimized in the manual synthesis of 18 F-FDHT to avoid cryogenic conditions (Zhou et al, 2014). Under this protocol the reduction step was performed at room temperature in ethanol and was complete after 10 min.…”

Section: Discussionmentioning

confidence: 99%

Fully-automated synthesis of 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

Lazari

Lyashchenko

Burnazi

et al. 2015

Applied Radiation and Isotopes

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Noninvasive in vivo imaging of androgen receptor (AR) levels with positron emission tomography (PET) is becoming the primary tool in prostate cancer detection and staging. Of the potential 18F-labeled PET tracers, 18F-FDHT has clinically shown to be of highest diagnostic value. We demonstrate the first automated synthesis of 18F-FDHT by adapting the conventional manual synthesis onto the fully-automated ELIXYS radiosynthesizer. Clinically-relevant amounts of 18F-FDHT were synthesized on ELIXYS in 90 min with decay-corrected radiochemical yield of 29 ± 5% (n = 7). The specific activity was 4.6 Ci/µmol (170 GBq/µmol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated 18F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use.

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Section: Discussionmentioning

confidence: 99%

Fully-automated synthesis of 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

Lazari

Lyashchenko

Burnazi

et al. 2015

Applied Radiation and Isotopes

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“…[ 18 F]FES and [ 18 F]FFNP were synthesized using optimized methods as described previously (5, 14, 16, 17). The specific activities for both [ 18 F]FES and [ 18 F]FFNP averaged 7700 ± 3000 Ci/mmol (average ± SEM).…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Noninvasive Imaging of Progesterone Receptor as a Predictive Biomarker of Tumor Responsiveness to Estrogen Deprivation Therapy

Chan

Fowler

Allen

et al. 2015

Clinical Cancer Research

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Purpose To investigate whether longitudinal functional PET imaging of mammary tumors using the radiopharmaceuticals [18F]FDG (to measure glucose uptake), [18F]FES (to measure estrogen receptor (ER) levels), or [18F]FFNP (to measure progesterone receptor (PgR) levels) is predictive of response to estrogen deprivation therapy. Experimental Design [18F]FDG, [18F]FES and [18F]FFNP uptake in endocrine-sensitive and -resistant mammary tumors was quantified serially by PET before ovariectomy or estrogen withdrawal in mice, and on days 3 and 4 after estrogen deprivation therapy. Specificity of [18F]FFNP uptake in ERα+ mammary tumors was determined by competition assay using unlabeled ligands for PgR or glucocorticoid receptor (GR). PgR expression was also assayed by immunohistochemistry (IHC). Results The levels of [18F]FES and [18F]FDG tumor uptake remained unchanged in endocrine-sensitive tumors after estrogen deprivation therapy compared to those at pre-treatment. In contrast, estrogen deprivation therapy led to a reduction in PgR expression and [18F]FFNP uptake in endocrine-sensitive tumors, but not in endocrine-resistant tumors, as early as 3 days post-treatment; the changes in PgR levels were confirmed by IHC. Unlabeled PgR ligand R5020 but not GR ligand dexamethasone blocked [18F]FFNP tumor uptake, indicating that [18F]FFNP bound specifically to PgR. Therefore, a reduction in FFNP tumor to muscle ratio in mammary tumors predicts sensitivity to estrogen deprivation therapy. Conclusions Monitoring the acute changes in ERα activity by measuring [18F]FFNP uptake in mammary tumors predicts tumor response to estrogen deprivation therapy. Longitudinal noninvasive PET imaging using [18F]FFNP is a robust and effective approach to predict tumor responsiveness to endocrine treatment.

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“…It has high relative binding affinity to PR, low nonspecific binding, and thus a high binding selectivity index (34, 35). Recently optimized and automated synthesis methods result in a final product with good yield (up to 77%), high radiochemical purity, and high specific activity (1300–8500 mCi/μmol) (36). Tissue biodistribution studies in estrogen-primed female rats demonstrated high PR-selective uptake in the uterus and ovaries (34).…”

Section: Progesterone Receptor Imagingmentioning

confidence: 99%

Imaging Diagnostic and Therapeutic Targets: Steroid Receptors in Breast Cancer

et al. 2016

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Estrogen receptor-alpha (ERα) and progesterone receptor (PR) are important steroid hormone receptor biomarkers used to determine prognosis and predict benefit from endocrine therapies for breast cancer patients. Receptor expression is routinely measured in biopsy specimens using immunohistochemistry, although such testing can be challenging particularly in the setting of metastatic disease. ERα and PR can be quantitatively assayed non-invasively with positron emission tomography (PET). This approach provides the opportunity to assess receptor expression and function in “real-time”, within the entire tumor, and across distant sites of metastatic disease. This article reviews the current evidence of ERα and PR PET imaging as predictive and early response biomarkers for endocrine therapy.

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Optimization of the preparation of fluorine‐18‐labeled steroid receptor ligands 16alpha‐[¹⁸F]fluoroestradiol (FES), [¹⁸F]fluoro furanyl norprogesterone (FFNP), and 16beta‐[¹⁸F]fluoro‐5alpha‐dihydrotestosterone (FDHT) as radiopharmaceuticals

Cited by 34 publications

References 29 publications

Fully-automated synthesis of 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

Fully-automated synthesis of 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

Longitudinal Noninvasive Imaging of Progesterone Receptor as a Predictive Biomarker of Tumor Responsiveness to Estrogen Deprivation Therapy

Imaging Diagnostic and Therapeutic Targets: Steroid Receptors in Breast Cancer

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