[<sup>123</sup>I]CC1: A PARP-Targeting, Auger Electron–Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Chan, Chung Ying; Chen, Zijun; Guibbal, Florian; Dias, Gemma; Destro, Gianluca; O’Neill, Edward; Veal, Mathew; Lau, Doreen; Mosley, Michael; Wilson, Thomas C.; Gouverneur, Véronique; Cornelissen, Bart

doi:10.2967/jnumed.123.265429

Cited by 10 publications

(3 citation statements)

References 42 publications

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“…To date, the diagnostic radiopharmaceuticals targeting PARP-1 that have been reported for SPECT/CT are 123 I-labeled olaparib ([ 123 I]I-PARPi ([ 123 I]5), [ 123 I]I-MAPi, − [ 123 I]CC1), and rucaparib ([ 123 I]GD1). Their common feature is that the radiolabeling methods are relatively complex, time-consuming, and require purification, and all of them are cleared via the hepatobiliary pathway.…”

Section: Discussionmentioning

confidence: 99%

Preparation and Evaluation of a Novel ^99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

Wang,

Feng,

Jiang

et al. 2024

Mol. Pharmaceutics

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Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [ 99m Tc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro. In HeLa cell experiments, the uptake of [ 99m Tc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumorbearing mice, [ 99m Tc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [ 99m Tc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [ 99m Tc]Tc-CNPN is a promising tumor imaging agent that targets PARP.

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Section: Discussionmentioning

confidence: 99%

Preparation and Evaluation of a Novel ^99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

Wang,

Feng,

Jiang

et al. 2024

Mol. Pharmaceutics

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“…A recently published paper by Chan et al investigated the effectiveness of another radio-iodinated PARP-ligand, namely [ 123 I]I-CC1, in three tumor cell lines (PSN1, U87MG, and MDA-MD-231) derived from pancreatic cancer, glioblastoma, and breast cancer, respectively [31]. The radiotoxic effect of [ 123 I]I-CC1 was assessed in cell cultures of all three tumor cell lines, while biodistribution studies were carried out by dynamic SPECT/CT over 1 h after intravenous injection in mouse models subcutaneously implanted with tumor-derived xenografts.…”

Section: Pancreatic Cancermentioning

confidence: 99%

PARP-Targeted Radiotheranostics with Auger Electrons: An Updated Overview

Filippi,

Urso,

Evangelista

2024

CIMB

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Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

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“…For the radiosynthesis of 10 , the reaction proceeded slowly at RT but was completed quickly after heating at 90 °C. Under similar conditions (except using 10:1 MeCN/water as solvent and a minimum amount of NaOH), the radiosynthesis of [ 123 I] 11 with [ 123 I]NaI was completed within 1 min at RT, indicating the DG assistance in this reaction and suggesting its extended application beyond CMRF, such as the radiosynthesis of [ 123 I]CC1, an 123 I-derivative of olaparib for Auger radiotherapy.…”

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confidence: 93%

Exploration of Directing-Group-Assisted, Copper-Mediated Radiofluorination and Radiosynthesis of [¹⁸F]Olaparib

Zhou,

Chu,

Chen

et al. 2023

ACS Med. Chem. Lett.

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Copper-mediated radiofluorination (CMRF) of organoboronic precursors is the method of choice for late-stage radiofluorination of aromatic compounds as positron emission tomography (PET) radiotracers. However, CMRF generally requires harsh reaction conditions, a large amount of substrates, and harsh solvents (e.g., DMA) to proceed, affording variable radiochemical yields (RCYs). Using [ 18 F]tosyl fluoride as the source of [ 18 F]fluoride, we have found a highly efficient CMRF of organoboronic precursors, assisted by a directing group (DG) at the ortho position. The reaction can be carried out under mild conditions (even at room temperature) in acetonitrile and results in high RCYs, providing a novel strategy for the radiofluorination of aromatic compounds. The exploration of this strategy also provided more information about side reactions in CMRF. Using this strategy, [ 18 F]olaparib has been radiosynthesized in high RCYs, with high molar activity and high chemical and radiochemical purities, demonstrating the great potential of DG-assisted CMRF in the preparation of 18 F-labeled PET radiotracers.

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[¹²³I]CC1: A PARP-Targeting, Auger Electron–Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Abstract: Pol y(adenosine diphosphate ribose) polymerase (PARP) inhibitors function as competitive inhibitors of the NAD 1 binding pocket of PARP enzymes, a class of DNA damage repair enzymes. They

Cited by 10 publications

References 42 publications

Preparation and Evaluation of a Novel ^99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

Preparation and Evaluation of a Novel ^99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

PARP-Targeted Radiotheranostics with Auger Electrons: An Updated Overview

Exploration of Directing-Group-Assisted, Copper-Mediated Radiofluorination and Radiosynthesis of [¹⁸F]Olaparib

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[123I]CC1: A PARP-Targeting, Auger Electron–Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Abstract: Pol y(adenosine diphosphate ribose) polymerase (PARP) inhibitors function as competitive inhibitors of the NAD 1 binding pocket of PARP enzymes, a class of DNA damage repair enzymes. They

Cited by 10 publications

References 42 publications

Preparation and Evaluation of a Novel 99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

Preparation and Evaluation of a Novel 99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

PARP-Targeted Radiotheranostics with Auger Electrons: An Updated Overview

Exploration of Directing-Group-Assisted, Copper-Mediated Radiofluorination and Radiosynthesis of [18F]Olaparib

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Product

Resources

About

[¹²³I]CC1: A PARP-Targeting, Auger Electron–Emitting Radiopharmaceutical for Radionuclide Therapy of Cancer

Preparation and Evaluation of a Novel ^99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

Preparation and Evaluation of a Novel ^99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent

Exploration of Directing-Group-Assisted, Copper-Mediated Radiofluorination and Radiosynthesis of [¹⁸F]Olaparib