Estrogen Receptor Ligands for Targeting Breast Tumours: A Brief Outlook on Radioiodination Strategies

Oliveira, Maria Cristina de; Neto, Carina; Gano, Lurdes; Marques, Fernanda; Santos, Isabel Cristina Ramos Vieira; Thiemann, Thies; Santos, Ana Cristina; Botelho, Maria Filomena; Oliveira, Carlos

doi:10.2174/1874471011205020124

Cited by 8 publications

(4 citation statements)

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“…There has been a significant advancement in the development of estrogen based radiopharmaceuticals for single photon emission computed tomography (SPECT) − or positron emission tomography (PET). , The well-known PET agent, 16α- 18 F-17β-estradiol ( 18 F-FES), has demonstrated promising results in the evaluation of estrogen-dependent tumors. It is currently in phase II trials for the prediction of response to antihormonal therapy in patients with ER(+) tumors.…”

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confidence: 99%

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas

et al. 2016

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The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind (99m)Tc. The radiolabeled complex, (99m)Tc-(EST)2DT was obtained in >99% radiochemical purity and 20-48 GBq/μmol of specific activity. RBA assay revealed ∼15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER-mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ∼6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(-) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 μM which was comparable to tamoxifen. The anticancer activity of the ligand is possibly due to the increase in ERβ and suppression of ERα protein levels in gene transcription. The studies reveal the potential of (EST)2DT as diagnostic imaging agent with the additional benefits in therapy.

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confidence: 99%

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas

et al. 2016

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“…Combined with highly selective and specific ER probes, it is possible to distinguish between ER-positive and ER-negative lesions in a noninvasive manner and accurately locate primary and metastatic tumors by using nuclear medicine imaging technology . Single-photon emission computed tomography (SPECT) imaging technology remains an indispensable approach for routine diagnostics and has been used for ER-targeted breast tumor imaging with radioactive iodide estradiol derivatives several decades ago. − …”

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confidence: 99%

“…Estradiol is a natural estrogen with a high ER affinity ( K d < 0.1 nM); the modification of estradiol, such as methoxy, fluorine, and acetylene groups at the 7α or 17α-position, was applied to improve the ER affinity and in vivo metabolic stability of a probe . The first radioiodinated SPECT agent 6α-[ 125 I]iodoestradiol was reported with high rat uterus uptake and target-to-nontarget ratio, while it was metabolized rapidly in vivo. , Other ER agents, such as 16α-[ 125 I]iodine-11β-methoxy-17β-estradiol ([ 125 I]MIE), 16α-[ 123 I]iodovinylestradiol ([ 123 I]IES), and (20Z)-11β-methoxy-17-α-[ 123 I]iodovinylestradiol (Z-[ 123 I]MIVE), have been reported and well-studied in animals and/or patients. − Almost all of these tracers exhibited rapid metabolism and low sex hormone-binding globulin (SHBG) binding. − In our group, we tried to introduce a 131 I-labeled 4-( p -iodophenyl) butyric acid group to ethinylestradiol ([ 131 I]IPBA-EE) to slow down the metabolism via albumin protection in vivo .…”

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“…Steroidal ligands could be readily radioiodinated through plenty of known classical labeling methods; however, only a few of them could be prepared with good radiolabeling yields and high specific activity. In our study, novel type 131 I-labeled ER-targeting estrogen derivatives [ 131 I]EITE and [ 131 I]MITE were successfully prepared with considerable radiolabeling yield (71.49 ± 0.56% and 31.02 ± 1.32%) and high specific activity (12.45 ± 3.16 and 20.02 ± 4.23 GBq/μmol) by a one-step “click” radioiodinated process.…”

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confidence: 99%

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Radioiodinated Ethinylestradiol Derivatives for Estrogen Receptor Targeting Breast Cancer Imaging

Liu

Lin

et al. 2022

ACS Med. Chem. Lett.

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Two novel PEGylated ethinylestradiol (PEG = poly(ethylene glycol)) estrogen receptor (ER) targeting probes [131I]EITE and [131I]MITE were synthesized and evaluated. Both probes had a nanomolar binding affinity to the ER receptor (36.47 nM for [131I]EITE and 61.83 nM for [131I]MITE). They showed high uptake in ER-positive MCF-7 cells and tumors, which could be significantly blocked by a coinjection of excess estradiol. Their ER specificities were further demonstrated by the low uptake in ER-negative MDA-MB-231 cells and tumors. The maximum tumor-to-muscle (T/M) ratios reach to 6.59 for [131I]EITE at 1 h postinjection (p.i.) and to 3.69 for [131I]MITE at 2 h p.i. in MCF-7 tumors. Among these two probes, [131I]EITE showed a faster tumor accumulation and a higher T/M ratio indicating it could be a better candidate for the potential diagnosis of ER-positive breast cancers.

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Progesterone receptor targeting with radiolabelled steroids: An approach in predicting breast cancer response to therapy

Cunha¹,

Gano²,

Morais³

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

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Estrogen Receptor Ligands for Targeting Breast Tumours: A Brief Outlook on Radioiodination Strategies

Cited by 8 publications

References 0 publications

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas

Radioiodinated Ethinylestradiol Derivatives for Estrogen Receptor Targeting Breast Cancer Imaging

Progesterone receptor targeting with radiolabelled steroids: An approach in predicting breast cancer response to therapy

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