Syntheses and preliminary evaluation of [<sup>18</sup>F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Li, Yesen; Zhang, Deliang; Shi, Ying; Guo, Zhide; Wu, Xinying; Ren, Jianlin; Zhang, Xianzhong; Wu, Hua

doi:10.1002/cmmi.1688

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…In addition, the uptake of Po-12-Cy5 the kidney was higher than that in other organs, indicating that the kidney may be the main excretion route. This is consistent with what has been reported in a series of other literatures (39)(40)(41). These results indicate that Po-12-Cy5 has a good targeting effect on TIGIT in HCC and can be used as an important indicator of changes in the immune microenvironment in HCC.…”

Section: Discussionsupporting

confidence: 92%

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

et al. 2023

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IntroductionHepatocellular carcinoma (HCC) has very poor prognosis due to its immunosuppressive properties. An effective measure to regulate tumor immunity is brachytherapy, which uses 125I seeds planted into tumor. T cell immune receptors with immunoglobulin and ITIM domains (TIGIT) is highly expressed in HCC. The TIGIT-targeted probe is expected to be an effective tool for indicating immunomodulation of 125I seed brachytherapy in HCC. In this study, We constructed a novel peptide targeting TIGIT to evaluate the immune regulation of 125I seed brachytherapy for HCC by near-infrared fluorescence (NIRF).MethodsExpression of TIGIT by immunofluorescence (IF) and flow cytometry (FCM) in different part and different differentiated human liver cancer tissues was verified. An optical fluorescence probe (Po-12) containing a NIRF dye and TIGIT peptide was synthesized for evaluating the modulatory effect of 125I seed brachytherapy. Lymphocytes uptake by Po-12 were detected by FCM and confocal microscopy. The distribution and accumulation of Po-12 in vivo were explored by NIRF imaging in subcutaneous and orthotopic tumors. IHC and IF staining were used to verify the expression of TIGIT in the tumors.ResultsTIGIT was highly expressed in HCC and increased with tumor differentiation. The dye-labeled peptide (Po-12) retained a stable binding affinity for the TIGIT protein in vitro. Accumulation of fluorescence intensity (FI) increased with time extended in subcutaneous H22 tumors, and the optimal point is 1 h. TIGIT was highly expressed on lymphocytes infiltrated in tumors and could be suppressed by 125I seed brachytherapy. Accumulation of Po-12-Cy5 was increased in tumor-bearing groups while declined in 125I radiation group.

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Section: Discussionsupporting

confidence: 92%

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

et al. 2023

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“…Li et al evaluated [ 18 F]AlF-NOTA (5) -G-TMTP1 as a PET probe in four different human hepatocellular carcinoma xenograft models [139]. Indeed, this linear hexapeptide displayed an important affinity for a series of highly metastatic tumor cells, though its binding mechanism is still unclear [140].…”

Section: Overview Of [18f]alf-labeled Molecules Conjugated To Chelmentioning

confidence: 99%

A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

et al. 2019

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Due to its ideal physical properties, fluorine-18 turns out to be a key radionuclide for positron emission tomography (PET) imaging, for both preclinical and clinical applications. However, usual biomolecules radiofluorination procedures require the formation of covalent bonds with fluorinated prosthetic groups. This drawback makes radiofluorination impractical for routine radiolabeling, gallium-68 appearing to be much more convenient for the labeling of chelator-bearing PET probes. In response to this limitation, a recent expansion of the 18F chemical toolbox gave aluminum [18F]fluoride chemistry a real prominence since the late 2000s. This approach is based on the formation of an [18F][AlF]2+ cation, complexed with a 9-membered cyclic chelator such as NOTA, NODA or their analogs. Allowing a one-step radiofluorination in an aqueous medium, this technique combines fluorine-18 and non-covalent radiolabeling with the advantage of being very easy to implement. Since its first reports, [18F]AlF radiolabeling approach has been applied to a wide variety of potential PET imaging vectors, whether of peptidic, proteic, or small molecule structure. Most of these [18F]AlF-labeled tracers showed promising preclinical results and have reached the clinical evaluation stage for some of them. The aim of this report is to provide a comprehensive overview of [18F]AlF labeling applications through a description of the various [18F]AlF-labeled conjugates, from their radiosynthesis to their evaluation as PET imaging agents.

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“…17,18 [ 18 F]AlF-NOTA-G-TMTP1 demonstrated high tumor/muscle (T/M) ratio and low liver uptake with excessively fast blood clearance. 19 Specific PET tracers with proper pharmacokinetics and pharmacodynamics are still in the open request for the early and precise detection of HCC.…”

Section: ■ Introductionmentioning

confidence: 99%

⁶⁸Ga-Labeled TMTP1 Derivatives with Moderate Hydrophilicity for Positron Emission Tomography of Hepatocellular Carcinoma in High Contrast

Fan

Wang

et al. 2023

J. Med. Chem.

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The reported specific positron emission tomography (PET) probes for the diagnosis of highly metastatic hepatocellular carcinoma (HCC) suffer from excessively high background uptake and fast blood clearance. Herein, five 68 Ga-labeled polyethylene glycol (PEG)-modified derivatives of the TMTP1 peptide were synthesized. The log D values decreased from −1.70 (non-PEGylated) to −1.97 to −2.94 corresponding to the increase of PEG chain length. Subnanomolar and nanomolar affinities comparable to the non-PEGylated TMTP1 derivative were revealed by the IC 50 values in SMMC-7721 cells.[ 68 Ga]Ga-NOTA-PEG 2 -TMTP1 presented a significantly higher tumor/liver ratio (4.19 ± 0.54, at 30 min post intravenous injection) and tumor/muscle ratio (2.14 ± 0.17) compared to the others and the previously radiolabeled TMTP1 derivatives. Small HCC lesions (<2 mm) in situ were detected with high tumor/liver ratio and low tumor/muscle ratio. The improved pharmacokinetics and blood clearance rate of 68 Ga-labeled TMTP1 derivatives indicated that moderate hydrophilicity due to PEGylation contributed to highcontrast PET of HCC.

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Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Cited by 15 publications

References 32 publications

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

⁶⁸Ga-Labeled TMTP1 Derivatives with Moderate Hydrophilicity for Positron Emission Tomography of Hepatocellular Carcinoma in High Contrast

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Syntheses and preliminary evaluation of [18F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

Cited by 15 publications

References 32 publications

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

Identification of a novel peptide targeting TIGIT to evaluate immunomodulation of 125I seed brachytherapy in HCC by near-infrared fluorescence

A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

68Ga-Labeled TMTP1 Derivatives with Moderate Hydrophilicity for Positron Emission Tomography of Hepatocellular Carcinoma in High Contrast

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Syntheses and preliminary evaluation of [¹⁸F]AlF‐NOTA‐G‐TMTP1 for PET imaging of high aggressive hepatocellular carcinoma

⁶⁸Ga-Labeled TMTP1 Derivatives with Moderate Hydrophilicity for Positron Emission Tomography of Hepatocellular Carcinoma in High Contrast