99m Tc-labeled estradiol as an estrogen receptor probe: Preparation and preclinical evaluation

Xia, Xiaotian; Feng, Hongyan; Li, Chongjiao; Qin, Chunxia; Song, Yun‐Chun; Zhang, Yongxue; Lan, Xiaoli

doi:10.1016/j.nucmedbio.2015.09.006

Cited by 21 publications

(16 citation statements)

References 34 publications

(43 reference statements)

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“…One key advantage of technetium comes from its rich chemical behavior that can assume a large spectrum of structural arrangements, the most important being the [Tc(CO) 3 ] + (carbonyl), [TcN] 2+ (nitrido), and [ReTcO] 3+ (oxo) cores (Arterburn, Corona, Rao, Carlson, & Katzenellenbogen, ; Mull, Sattigeri, Rodriguez, & Katzenellenbogen, ; Neto et al, ; Takahashi et al, ; Wüst, Spies, & Johannsen, ; Xia et al, ). The selection of the adequate combination of metal core and chelator is essential to allow a fine‐tuning of the physicochemical and biological properties of the resulting radiopharmaceutical (Bandoli, Dolmella, Porchia, Refosco, & Tisato, ; Bolzati et al, ; Pasqualini & Duatti, ).…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of a ^99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

et al. 2019

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The aim of this work was to develop and evaluate a 99m Tc-labeled neuropeptide Y derivative with affinity toward Y1-receptor. The selected amino acid sequence included nine amino acids derived from the C-terminal portion of the NPY complemented with the addition of one cysteine-mercaptoacetic acid moiety to bind the radiometal. Labeling was achieved through the preparation of a 3 + 1 nitrido complex. Physicochemical evaluation, cell uptake, internalization and externalization studies, and competitive assays were performed. Biodistribution experiments were carried out in normal and tumor-bearing mice. A single product with radiochemical purity >90% and high stability was obtained. In vitro analysis showed specific cellular uptake, IC 50 of 73.2 nM, and a high internalization rate (80%). Biodistribution studies showed low blood and renal uptake and combined hepatobiliary and urinary elimination. Preliminary studies in mice bearing induced breast tumors rendered promising uptake values. K E Y W O R D Sbreast cancer, neuropeptide Y, radiolabeling, scintigraphy, technetium

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Section: Introductionmentioning

confidence: 99%

Development and characterization of a ^99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

et al. 2019

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“…To meet the need for quantifiable imaging targeting to TSPO sites, we focused on linear polyaminopolycarboxylic acid chelating agents as metal ions binding agents. DTPA is known as an efficient chelating agent, and has been used as an MRI contrast agent as well as radiopharmaceuticals (37). Importantly, we introduced DTPA groups to enhance the water solubility of the TSPO probe and to minimize the intrahepatic metabolism.…”

Section: Discussionmentioning

confidence: 99%

99mTc-labeled TSPO ligand CB86 targeting macrophages for rheumatoid arthritis SPECT imaging and preliminary evaluation of anti-inflammatory effect

Liu¹,

Yang²,

Fu³

et al. 2019

Preprint

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Background and Objective TSPO (translocator protein, 18 kDa) is up-regulated in activated macrophages, and serves as an attractive target for macrophages molecular imaging. Previous studies showed that TSPO radiotracer can visualize arthritis via positron emission tomography (PET). Compared with PET, single photon emission computed tomography (SPECT) has several advantages, such as lower cost and commercial availability. The aim of the present study is to develop the 99mTc-labeled TSPO ligand CB86 as a novel SPECT probe for imaging of rheumatoid arthritis and preliminary evaluating the effectiveness of steroid anti-inflammatory therapy. Methods A novel TSPO ligand CB86 was linked to DTPAA and then labeled with 99mTc to obtain 99mTc-DTPA-CB86. The labeling efficiency, radiochemical purity, and stability were determined in vitro. In vitro cellular uptake, efflux and binding affinity of 99mTc-DTPA-CB86 to TSPO were performed on RAW264.7 macrophage cells. The distribution and SPECT studies were conducted on Freund’s Adjuvant-Induced Left Arthritis in rats after the injection of 99mTc-DTPA-CB86 with or without co-injection of unlabeled DTPA-CB86. Result The radiosynthesis of 99mTc-DTPA-CB86 was completed successfully with the labeling yields and radiochemical purity of 95.86 ± 2.45 % and 97.45 ± 0.69 %, respectively. 99mTc-DTPA-CB86 displayed good stability, which the radiochemical purity was more than > 90%, in the saline or mouse serum at 4 h. It also exhibited high specific TSPO binging in RAW264.7 macrophage cells in vitro. The highest uptake ratio was (36.45 ± 2.18) % at 3 h after incubation, and decreased significantly after adding excessive unlabeled DTPA-CB86. 99mTc-DTPA-CB86 bound to TSPO with low nanomolar affinity (IC50 =0.49 nM) in RAW264.7 cells. The cell efflux study showed that 99mTc-DTPA-CB86 has good cell retention by RAW264.7 cells, with only about 13.99 % (decreased from (33.31 ± 2.34) % to (19.32 ± 2.01) % of total input radioactivity) of 99mTc-DTPA-CB86 efflux observed during 4.5 h to 8 h incubation. Biodistribution studies showed the left inflammatory ankle uptake was 2.35±0.10 %ID/g, and the inflammatory ankle to muscle ratio was 3.01 ± 0.09 at 180 min after injection. Small animal SPET imaging studies revealed that 99mTc-DTPA-CB86 could clearly identify left inflammatory ankle with good contrast at 30-180 min after injection. Uptake of 99mTc-DTPA-CB86 in the inflammatory ankles could be largely blocked by an excess of unlabled DTPA-CB86. Furthermore, 99mTc-DTPA-CB86 accumulation in the left inflammatory ankles significantly decreased in RA rats treated with dexamethasone. Conclusion 99mTc-DTPA-CB86 can be readily synthesized, clearly visualized arthritis with low background and monitor therapy response of anti-inflammatory therapy, suggesting its potential as a novel promising molecular probe targeting TSPO for arthritic SPECT imaging. Key words TSPO (translocator protein, 18 kDa); Technetium radioisotope; SPECT imaging; Rheumatoid arthritis; Macrophages; Glucocorticoids.

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“…The use of estrogen radiopharmaceuticals to image estrogen receptor (ER) in vivo has the potential to determine the ER status of breast cancer. Fluorine‐18, iodine‐131, and other radionuclides are widely used to label estrogen derivatives for in vivo imaging of ER density in steroid‐sensitive tumors (Ali, Rousseau, Gantchev, & van Lier, 1993; Ali, Rousseau, Ghaffari, & van Lier, 1988; Ali et al, 2003; Antunes et al., 2017; Gatley, Shaughnessy, & Inhorn, & Leiberman, 1981; Hochberg, 1979; Huang, Li, Lv, Liu, & Lin, 2018; Kiesewetter et al., 1984; Lim, Zheng, Berridge, & Tewson, 1996; Linden et al., 2006; Mortimer et al., 1996; Nayak et al., 2008; Neto et al., 2012; Paquette et al., 2013; Rijks et al., 1998; Symes, Coulson, & Ralphs, 1985; VanBrocklin, Carlson, Katzenellenbogen, & Welch, 1993; Xia et al., 2015; Yan et al., 2013). Among them, the most successful 18 F‐labeled estrogen derivative, 16α‐[ 18 F]fluoro‐17β‐estradiol ([ 18 F]FES), has a good affinity for ER+ tumors and predicts response to tamoxifen (Linden et al., 2006; Mortimer et al., 1996).…”

Section: Introductionmentioning

confidence: 99%

Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging

Peng

Gao

et al. 2020

Chem Biol Drug Des

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The aim of this study was to develop a 1-(2-(2-(2-(1,2,3-triazol)ethoxy)ethoxy) ethyl)-5-[ 125/131 I]iodo-1,2,3-triazole-diestradiol ([ 125/131 I]ITE2), for estrogen receptor (ER)-expressing breast cancer imaging with single-photon emission computed tomography (SPECT). [ 125/131 I]ITE2 was prepared in good radiochemical yield (94.4 ± 0.4%) with high radiochemical purity (>99%). [ 125/131 I]ITE2 had good stability in vitro and moderate molar activity (0.3 ± 0.2 GBq/µmol). Higher uptake in ER-positive MCF-7 cells than that of ER-negative MDA-MB-231 cells was observed at all time points. Rats biodistribution showed that [ 131 I]ITE2 had high uptake in ERabundant uterine and ovarian (5.7 ± 0.4 and 10.1 ± 1.4%ID/g at 1 hr postinjection) and could be blocked by co-injection of estradiol (2.7 ± 0.1 and 5.5 ± 0.4%ID/g) obviously. In the SPECT/CT imaging study, [ 125 I]ITE2 showed significant higher uptake in MCF-7 tumor (3.1 ± 0.4%ID/g) than that of MDA-MB-231 (0.9 ± 0.1%ID/g). Furthermore, the specific uptake of [ 125 I]ITE2 in ER-positive MCF-7 tumor could be blocked effectively by preadministration of fulvestrant (1.2 ± 0.4%ID/g). A novel radioiodinated dimeric estrogen was designed and synthesized with promising ER targeting ability and specificity. It is worthy of further investigation to validate the advantages of the dimer in ER-positive breast cancer diagnosis.

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99m Tc-labeled estradiol as an estrogen receptor probe: Preparation and preclinical evaluation

Cited by 21 publications

References 34 publications

Development and characterization of a ^99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

Development and characterization of a ^99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

99mTc-labeled TSPO ligand CB86 targeting macrophages for rheumatoid arthritis SPECT imaging and preliminary evaluation of anti-inflammatory effect

Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging

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99m Tc-labeled estradiol as an estrogen receptor probe: Preparation and preclinical evaluation

Cited by 21 publications

References 34 publications

Development and characterization of a 99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

Development and characterization of a 99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

99mTc-labeled TSPO ligand CB86 targeting macrophages for rheumatoid arthritis SPECT imaging and preliminary evaluation of anti-inflammatory effect

Radioiodinated estradiol dimer for estrogen receptor targeted breast cancer imaging

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Development and characterization of a ^99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging

Development and characterization of a ^99mTc‐labeled Neuropeptide Y short analog with potential application in breast cancer imaging