Current status and progress in using radiolabelled PARP-1 inhibitors for imaging PARP-1 expression in tumours

Wang, Qianna; Zhang, Junbo

doi:10.1016/j.ejmech.2022.114690

Cited by 14 publications

(26 citation statements)

References 77 publications

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“…1 H NMR (300 MHz, DMSO-d 6 ) δ 8.31 (d, J = 2.8 Hz, 1H), 8.17 (t, J = 5.7 Hz, 1H), 7.85 (d, J = 1.7 Hz, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.47 (dd, J = 9.7, 4.4 Hz, 2H), 6.64 (t, J = 7.7 Hz, 1H), 6.25 (t, J = 4.0 Hz, 1H), 4.96 (t, J = 5.5 Hz, 1H), 4.22−3.99 (m, 2H), 3.74 (dd, J = 9.8, 5.3 Hz, 2H), 3.62− 3.49 (m, 2H), 3.31 (t, J = 6.5 Hz, 2H), 3.17 (d, J = 5.3 Hz, 1H). 13…”

Section: Synthesis 9-({5-[(2-hydroxyethylmentioning

confidence: 99%

“…1 H NMR (300 MHz, DMSO-d 6 ) δ 8.44 (s, 1H), 8.15 (t, J = 5.6 Hz, 1H), 7.97 (d, J = 2.3 Hz, 1H), 7.82 (dd, J = 8.0, 1.6 Hz, 1H), 7.45 (dd, J = 7.3, 1.7 Hz, 1H), 6.89 (d, J = 8.9 Hz, 1H), 6.62 (t, J = 7.7 Hz, 1H), 6.30 (t, J = 3.9 Hz, 1H), 4.87 (t, J = 5.5 Hz, 1H), 4.44−4.20 (m, 2H), 3.72−3.69 (m, 2H), 3.63− 3.50 (m, 2H), 3.32 (d, J = 6.1 Hz, 2H). 13…”

Section: -[(5-ethynylpyridin-2-yl)oxy]ethan-1-ol (4b)mentioning

confidence: 99%

“…1 H NMR (300 MHz, CDCl 3 ) δ 7.96 (d, J = 3.1 Hz, 1H), 7.25 (d, J = 8.7 Hz, 1H), 7.07 (dd, J = 8.7, 3.1 Hz, 1H), 4.12−4.01 (m, 2H), 3.83−3.67 (m, 3H), 3.67−3.52 (m, 6H), 3.52−3.41 (m, 2H). 13…”

Section: -(2-((6-(1-oxo-1234-tetrahydro-[14]diazepino[671-hi]indol-6-...mentioning

confidence: 99%

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Design, Synthesis, and Evaluation of [¹⁸F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

Zheng,

Huang,

Xie

et al. 2024

Mol. Pharmaceutics

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Compounds 8a−j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for highaffinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [ 18 F]FTT, [ 18 F]8a, [ 18 F]8d, and [ 18 F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [ 18 F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [ 18 F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [ 18 F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [ 18 F]BIBD-300 was greater than that of [ 18 F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [ 18 F]FTT, which mainly relies on hepatobiliary clearance, [ 18 F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [ 18 F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [ 18 F]FTT, [ 18 F]BIBD-300, and [ 18 F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [ 18 F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [ 18 F]FTT and [ 18 F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [ 18 F]FTT and [ 18 F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [ 18 F]BIBD-300 is a new option for an excellent PARP-1 tracer.

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Section: Synthesis 9-({5-[(2-hydroxyethylmentioning

confidence: 99%

Section: -[(5-ethynylpyridin-2-yl)oxy]ethan-1-ol (4b)mentioning

confidence: 99%

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Design, Synthesis, and Evaluation of [¹⁸F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

Zheng,

Huang,

Xie

et al. 2024

Mol. Pharmaceutics

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“…Radioligand therapy (RLT) is a technique used for antitumor therapy based on the combination of high-affinity molecules or materials to deliver radionuclides to cancer cells. − In contrast to external beam radiation therapy (EBRT), RLT administers the radioligand directly to the body through intravenous injection, allowing for targeted therapeutic applications to destroy tumor cells . Unlike chemotherapy, which mainly targets a specific protein in the malignancy signaling pathway, RLT targets specific membrane proteins that are overexpressed in malignancies and uses radiation toxicity to directly destroy tumor cell DNA, making it a promising and specific treatment option for tumor therapy with reduced risk for primary or acquired resistance. − Several radioligands have achieved great success in preclinical and clinical evaluation.…”

Section: Radioligand Therapy (Rlt)mentioning

confidence: 99%

Exploiting Albumin as a Versatile Carrier for Cancer Theranostics

Tao,

Jakobsson,

Chen

et al. 2023

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: "Theranostics" is a portmanteau that links the fields of therapeutics and diagnostics; it describes a personalized medical approach with the expectation to improve the prognosis for cancer patients while reducing the risk of adverse effects that is currently commonly seen for many systemic cancer therapies. Theranostic radioligands can deliver radionuclides to tumors in a targeted manner, achieving both diagnosis and irreversible damage to tumor cells. Compared with chemotherapy, a therapeutic radioligand that directly damages the DNA sequence of tumor cells is less likely to be impacted by chemotherapy resistance, making the use of a radioligand a promising cancer treatment modality. However, many novel radioligands do not have optimal pharmacokinetics and are rapidly cleared out of the body. Therefore, there has been a long-standing interest in the development of long-acting formulas with prolonged circulation half-life. Albumin, as the most abundant protein in human serum, plays a pivotal role as a physiological carrier protein of, e.g., fatty acids and hormones. Its attributes, including extended circulation time, biodegradability, nontoxicity, and absence of immunogenicity, render it an exceptional candidate as a carrier for various drugs including theranostic agents. In this regard, three prominent albumin-based drug delivery technologies have been developed: (1) coupling small molecule drugs to exogenous or endogenous albumin, (2) employing fusion technology to conjugate bioactive proteins with albumin, and (3) encapsulating drugs within albumin nanoparticles. Of these technologies, the strategy that conjugate radioligands to albumin binding molecules stands out as one of the most widely applied approaches due to its minimal adverse effects and high efficiency in prolonging blood retention time. The utilization of albumin as a carrier for theranostic radioligands holds significant promise in precision medicine and diagnostic procedures.In this Account, we describe the recent development of long-acting radioligands. First, we give a brief introduction to radioligand therapy including its advantages and current challenges, such as fast blood clearance. Subsequently, we briefly summarize the approaches to prolonging blood circulation time with a focus on the albumin binding strategy. We also comprehensively review the structure of human serum albumin, its binders, and efforts in discovering new albumin binders that can be utilized in developing theranostic radioligands. Furthermore, we review the recent progress of PSMA-targeting long-acting radioligands, summarizing the relevant structure−activity relationships (SARs). Lastly, we outline the probable issues in the future development of radioligands.Collectively, the albumin binders, PSMA-targeting radioligands, and relevant SARs from our studies could shed new light on the future development of different theranostic radioligands.

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“…The table below shows PARP7 enzyme inhibitory activity of exemplary compounds tested and the reported IC 50 . The pharmacokinetic properties were evaluated for selected compounds in mice following a single 100 mg/kg dose of 51 (121, F%), 84A (106, F%), and 85A (301, F%). …”

Section: Important Compound Classesmentioning

confidence: 99%

Recent Discovery of PARP7 Inhibitors as Anticancer Agents

Kargbo

2022

ACS Med. Chem. Lett.

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The 5-year survival rate for advanced ovarian cancer remains less than 30% and has not improved in recent years. Disclosures in this patent highlight provides PARP7 inhibitors and methods for treating cancers such as ovarian cancer and pancreatic cancers. Important Compound Classes. Title. Tricyclic Derivatives Useful as PARP7 InhibitorsPatent Publication Number. WO 2022/170974 A1 (URL:https://patentscope.wipo.int/search/en/detail. jsf?docId=WO2022170974&_cid=P10-L7CDOS-28964-1).

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Current status and progress in using radiolabelled PARP-1 inhibitors for imaging PARP-1 expression in tumours

Cited by 14 publications

References 77 publications

Design, Synthesis, and Evaluation of [¹⁸F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

Design, Synthesis, and Evaluation of [¹⁸F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

Exploiting Albumin as a Versatile Carrier for Cancer Theranostics

Recent Discovery of PARP7 Inhibitors as Anticancer Agents

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Current status and progress in using radiolabelled PARP-1 inhibitors for imaging PARP-1 expression in tumours

Cited by 14 publications

References 77 publications

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

Exploiting Albumin as a Versatile Carrier for Cancer Theranostics

Recent Discovery of PARP7 Inhibitors as Anticancer Agents

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Product

Resources

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Design, Synthesis, and Evaluation of [¹⁸F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

Design, Synthesis, and Evaluation of [¹⁸F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1