Design, synthesis, radiolabeling and biological evaluation of new urea-based peptides targeting prostate specific membrane antigen

Mosayebnia, Mona; Hajimahdi, Zahra; Beiki, Davood; Rezaeianpour, Maliheh; Hajiramezanali, Maliheh; Geramifar, Parham; Sabzevari, Omid; Amini, Mohsen; Hatamabadi, Dara; Shahhosseini, Soraya

doi:10.1016/j.bioorg.2020.103743

Cited by 15 publications

(12 citation statements)

References 47 publications

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“…Various PSMA inhibitor ligands were synthesized and labeled with different radioisotopes [ 27 ]. These agents also became available for scintigraphy and single-photon emission computed tomography (SPECT) tracers [ 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Targeting Agentsmentioning

confidence: 99%

“…PSMA is a metallopeptidase and a transmembrane glycoprotein overexpressed in PCa cell membranes, while PSA is a glycoprotein secreted into the lumen of prostatic ducts, which is over-released into the blood circulation following destruction of glandular architecture in PCa [ 14 ]. Meanwhile, 99m Tc-labeled tracers were also developed [ 15 , 16 , 17 , 18 , 19 , 20 ] to hypothetically provide PCa imaging cheaper and more extensively available.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends

Manafi‐Farid

Ranjbar

Araghi

et al. 2021

Cancers

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Accurate primary staging is the cornerstone in all malignancies. Different morphological imaging modalities are employed in the evaluation of prostate cancer (PCa). Regardless of all developments in imaging, invasive histopathologic evaluation is still the standard method for the detection and staging of the primary PCa. Magnetic resonance imaging (MRI) and computed tomography (CT) play crucial roles; however, functional imaging provides additional valuable information, and it is gaining ever-growing acceptance in the management of PCa. Targeted imaging with different radiotracers has remarkably evolved in the past two decades. [111In]In-capromab pendetide scintigraphy was a new approach in the management of PCa. Afterwards, positron emission tomography (PET) tracers such as [11C/18F]choline and [11C]acetate were developed. Nevertheless, none found a role in the primary staging. By introduction of the highly sensitive small molecule prostate-specific membrane antigen (PSMA) PET/CT, as well as recent developments in MRI and hybrid PET/MRI systems, non-invasive staging of PCa is being contemplated. Several studies investigated the role of these sophisticated modalities in the primary staging of PCa, showing promising results. Here, we recapitulate the role of targeted functional imaging. We briefly mention the most popular radiotracers, their diagnostic accuracy in the primary staging of PCa, and impact on patient management.

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Section: Targeting Agentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends

Manafi‐Farid

Ranjbar

Araghi

et al. 2021

Cancers

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show abstract

“…Hydrazinonicotinamide (HYNIC), which was first reported by Abrams et al [26] in the early 1990s, is an attractive bifunctional chelator that is widely used to couple with technetium-99m and form stable radiolabeled complexes [27][28][29][30][31][32]. In addition, with different co-ligands, such as tricine, ethylenediamine-N,N'-diacetic acid (EDDA) and triphenylphosphine sulfonates (TPPTS, trisodium triphenylphosphine-3,3 ,3 -trisulfonate; TPPDS, disodium triphenylphosphine-3,3 -disulfonate; and TPPMS, sodium triphenylphosphine-3monosulfonate), these radiotracers exhibited obvious diverse results in terms of biodistribution and lipophilicity, and many studies have been reported to date [33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia

et al. 2021

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To develop novel 99mTc-labeled single-photon emission computed tomography (SPECT) radiotracers for imaging hypoxia, a novel HYNICNM ligand (6-hydrazinonicotinamide (HYNIC) 2-nitroimidazole derivative) was designed and synthesized. It was radiolabeled with technetium-99m using tricine/trisodium triphenylphosphine-3,3′,3′′-trisulfonate (TPPTS), tricine/sodium triphenylphosphine-3-monosulfonate (TPPMS) and tricine as co-ligands to obtain [99mTc]Tc-tricine-TPPTS-HYNICNM, [99mTc]Tc-tricine-TPPMS-HYNICNM, and [99mTc]Tc-(tricine)2-HYNICNM, respectively. The three technetium-99m complexes were radiolabeled in one step with a high yield (95%) and had good stability in saline and mouse serum. In vitro cellular uptake results showed that these complexes exhibited good hypoxic selectivity. The partition coefficient indicated that they were good hydrophilic complexes, and [99mTc]Tc-tricine-TPPTS-HYNICNM displayed the highest hydrophilicity (-3.02 ± 0.08). The biodistribution in mice bearing S180 tumors showed that [99mTc]Tc-tricine-TPPTS-HYNICNM exhibited higher tumor uptake (1.05 ± 0.27% IA/g); more rapid clearance from the liver, blood, muscle, and other non-target organs; and a higher tumor/non-target ratio, especially for the tumor/liver ratio (1.95), than [99mTc]Tc-tricine-TPPMS-HYNICNM and [99mTc]Tc-(tricine)2-HYNICNM. The results of single-photon emission computed tomography (SPECT) imaging studies of [99mTc]Tc-tricine-TPPTS-HYNICNM were in accordance with the biodistribution results, which suggested that [99mTc]Tc-tricine-TPPTS-HYNICNM is a promising agent for imaging tumor hypoxia.

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“…Both new cases and deaths as a result of prostate cancer have been on the rise in recent years [2]. Most prostate cancer patients with a 15% 5-year survival rate died from tumor progression in the late stage [3]. Hence, the early diagnosis of prostate cancer and detection of recurrent lesions have become one of the focuses of clinical attention all over the world [4].…”

Section: Introductionmentioning

confidence: 99%

Preparation and Biological Evaluation of [99mTc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer

et al. 2020

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Prostate-specific membrane antigen (PSMA) is a well-established biological target that is overexpressed on the surface of prostate cancer lesions. Radionuclide-labeled small-molecule PSMA inhibitors have been shown to be promising PSMA-specific agents for the diagnosis and therapy of prostate cancer. In this study, a glutamate-urea-based PSMA-targeted ligand containing an isonitrile (CNGU) was synthesized and labeled with 99mTc to prepare [99mTc]Tc-CNGU with a high radiochemical purity (RCP). The CNGU ligand showed a high affinity toward PSMA (Ki value is 8.79 nM) in LNCaP cells. The [99mTc]Tc-CNGU exhibited a good stability in vitro and hydrophilicity (log P = −1.97 ± 0.03). In biodistribution studies, BALB/c nude mice bearing LNCaP xenografts showed that the complex had a high tumor uptake with 4.86 ± 1.19% ID/g, which decreased to 1.74 ± 0.90% ID/g after a pre-injection of the selective PSMA inhibitor ZJ-43, suggesting that it was a PSMA-specific agent. Micro-SPECT imaging demonstrated that the [99mTc]Tc-CNGU had a tumor uptake and that the uptake was reduced in the image after blocking with ZJ-43, further confirming its PSMA specificity. All of the results in this work indicated that [99mTc]Tc-CNGU is a promising PSMA-specific tracer for the imaging of prostate cancer.

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Design, synthesis, radiolabeling and biological evaluation of new urea-based peptides targeting prostate specific membrane antigen

Cited by 15 publications

References 47 publications

Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends

Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends

Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia

Preparation and Biological Evaluation of [99mTc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer

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