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  1. Article ; Online: Sensitive Positron Emission Tomography Imaging of PD-L1 Expression in Human Breast and Lung Carcinoma Xenografts Using the Radiometalated Peptide Ga-68-TRAP-WL12.

    Quigley, Neil Gerard / Steiger, Katja / Färber, Stefanie Felicitas / Richter, Frauke / Weichert, Wilko / Notni, Johannes

    Molecular pharmaceutics

    2024  Volume 21, Issue 4, Page(s) 1827–1837

    Abstract: Noninvasive imaging of the immune checkpoint protein programmed death ligand 1 (PD-L1; synonyms: CD274, B7-H1) holds great promise to improve patient selection and, thus, response rates for immune checkpoint therapy (ICT) with monoclonal antibodies ... ...

    Abstract Noninvasive imaging of the immune checkpoint protein programmed death ligand 1 (PD-L1; synonyms: CD274, B7-H1) holds great promise to improve patient selection and, thus, response rates for immune checkpoint therapy (ICT) with monoclonal antibodies targeting the PD1/PD-L1 axis. The PD-L1 specific peptide WL12 (cyclo(AcY-(
    MeSH term(s) Humans ; Animals ; Mice ; Gallium Radioisotopes/chemistry ; B7-H1 Antigen/metabolism ; Heterografts ; Tissue Distribution ; Peptides/chemistry ; Lung Neoplasms/diagnostic imaging ; Cell Line, Tumor ; Adenocarcinoma of Lung ; Positron-Emission Tomography/methods ; Lung/metabolism
    Chemical Substances Gallium-68 (98B30EPP5S) ; Gallium Radioisotopes ; B7-H1 Antigen ; Peptides
    Language English
    Publishing date 2024-01-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.3c01128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Complexity of αvβ6-integrin targeting RGD peptide trimers: emergence of non-specific binding by synergistic interaction.

    Quigley, Neil Gerard / Richter, Frauke / Kossatz, Susanne / Notni, Johannes

    RSC medicinal chemistry

    2023  Volume 14, Issue 12, Page(s) 2564–2573

    Abstract: Multimerization is an established strategy to design bioactive macromolecules with enhanced avidity, which has been widely employed to increase the target-specific binding and uptake of imaging probes and pharmaceuticals. However, the factors governing ... ...

    Abstract Multimerization is an established strategy to design bioactive macromolecules with enhanced avidity, which has been widely employed to increase the target-specific binding and uptake of imaging probes and pharmaceuticals. However, the factors governing the general biodistribution of multimeric probes are less well understood but are nonetheless decisive for their clinical application. We found that regiospecific exchange of phenylalanine by tyrosine (chemically equivalent to addition of single oxygen atoms) can have an unexpected, dramatic impact on the
    Language English
    Publishing date 2023-09-28
    Publishing country England
    Document type Journal Article
    ISSN 2632-8682
    ISSN (online) 2632-8682
    DOI 10.1039/d3md00365e
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: PET/CT imaging of pancreatic carcinoma targeting the "cancer integrin" αvβ6.

    Quigley, Neil Gerard / Czech, Norbert / Sendt, Wolfgang / Notni, Johannes

    European journal of nuclear medicine and molecular imaging

    2021  Volume 48, Issue 12, Page(s) 4107–4108

    MeSH term(s) Antigens, Neoplasm ; Cell Line, Tumor ; Humans ; Integrins ; Pancreatic Neoplasms/diagnostic imaging ; Positron Emission Tomography Computed Tomography ; Pancreatic Neoplasms
    Chemical Substances Antigens, Neoplasm ; Integrins
    Language English
    Publishing date 2021-06-09
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-021-05443-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Tracking a TGF-β activator in vivo: sensitive PET imaging of αvβ8-integrin with the Ga-68-labeled cyclic RGD octapeptide trimer Ga-68-Triveoctin.

    Quigley, Neil Gerard / Steiger, Katja / Richter, Frauke / Weichert, Wilko / Hoberück, Sebastian / Kotzerke, Jörg / Notni, Johannes

    EJNMMI research

    2020  Volume 10, Issue 1, Page(s) 133

    Abstract: Purpose: As a major activator of transforming growth factor β (TGF-β), the RGD receptor αvβ8-integrin is involved in pathogenic processes related to TGF-β dysregulation, such as tumor growth, invasion, and radiochemoresistance, metastasis and tumor cell ...

    Abstract Purpose: As a major activator of transforming growth factor β (TGF-β), the RGD receptor αvβ8-integrin is involved in pathogenic processes related to TGF-β dysregulation, such as tumor growth, invasion, and radiochemoresistance, metastasis and tumor cell stemness, as well as epithelial-mesenchymal transition. The novel positron emission tomography (PET) radiopharmaceutical Ga-68-Triveoctin for in vivo mapping of αvβ8-integrin expression might enhance the prognosis of certain tumor entities, as well as support and augment TGF-β-targeted therapeutic approaches.
    Methods: Monomeric and trimeric conjugates of cyclo(GLRGDLp(NMe)K(pent-4-ynoic amide)) were synthesized by click chemistry (CuAAC), labeled with Ga-68, and evaluated in MeWo (human melanoma) xenografted SCID mice by means of PET and ex-vivo biodistribution. αvβ8-integrin expression in murine tissues was determined by β8-IHC. A human subject received a single injection of 173 MBq of Ga-68-Triveoctin and underwent 3 subsequent PET/CT scans at 25, 45, and 90 min p.i..
    Results: The trimer Ga-68-Triveoctin exhibits a 6.7-fold higher αvβ8-integrin affinity than the monomer (IC
    Conclusion: Ga-68-Triveoctin enables sensitive in-vivo imaging αvβ8-integrin expression in murine tumor xenografts. PET in a human subject confirmed a favorable biodistribution, underscoring the potential of Ga-68-Triveoctin for mapping of αvβ8-integrin expression in a clinical setting.
    Language English
    Publishing date 2020-10-31
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2619892-7
    ISSN 2191-219X
    ISSN 2191-219X
    DOI 10.1186/s13550-020-00706-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: There is a world beyond αvβ3-integrin: Multimeric ligands for imaging of the integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1 by positron emission tomography.

    Steiger, Katja / Quigley, Neil Gerard / Groll, Tanja / Richter, Frauke / Zierke, Maximilian Alexander / Beer, Ambros Johannes / Weichert, Wilko / Schwaiger, Markus / Kossatz, Susanne / Notni, Johannes

    EJNMMI research

    2021  Volume 11, Issue 1, Page(s) 106

    Abstract: Background: In the context of nuclear medicine and theranostics, integrin-related research and development was, for most of the time, focused predominantly on 'RGD peptides' and the subtype αvβ3-integrin. However, there are no less than 24 known ... ...

    Abstract Background: In the context of nuclear medicine and theranostics, integrin-related research and development was, for most of the time, focused predominantly on 'RGD peptides' and the subtype αvβ3-integrin. However, there are no less than 24 known integrins, and peptides without the RGD sequence as well as non-peptidic ligands play an equally important role as selective integrin ligands. On the other hand, multimerization is a well-established method to increase the avidity of binding structures, but multimeric radiopharmaceuticals have not made their way into clinics yet. In this review, we describe how these aspects have been interwoven in the framework of the German Research Foundation's multi-group interdisciplinary funding scheme CRC 824, yielding a series of potent PET imaging agents for selective imaging of various integrin subtypes.
    Results: The gallium-68 chelator TRAP was utilized to elaborate symmetrical trimers of various peptidic and non-peptidic integrin ligands. Preclinical data suggested a high potential of the resulting Ga-68-tracers for PET-imaging of the integrins α5β1, αvβ8, αvβ6, and αvβ3. For the first three, we provide some additional immunohistochemistry data in human cancers, which suggest several future clinical applications. Finally, application of αvβ3- and αvβ6-integrin tracers in pancreatic carcinoma patients revealed that unlike αvβ3-targeted PET, αvβ6-integrin PET is not characterized by off-target uptake and thus, enables a substantially improved imaging of this type of cancer.
    Conclusions: Novel radiopharmaceuticals targeting a number of different integrins, above all, αvβ6, have proven their clinical potential and will play an increasingly important role in future theranostics.
    Language English
    Publishing date 2021-10-12
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 2619892-7
    ISSN 2191-219X
    ISSN 2191-219X
    DOI 10.1186/s13550-021-00842-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: PET/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the "Cancer Integrin" αvβ6 with Ga-68-Trivehexin.

    Quigley, Neil Gerard / Steiger, Katja / Hoberück, Sebastian / Czech, Norbert / Zierke, Maximilian Alexander / Kossatz, Susanne / Pretze, Marc / Richter, Frauke / Weichert, Wilko / Pox, Christian / Kotzerke, Jörg / Notni, Johannes

    European journal of nuclear medicine and molecular imaging

    2021  Volume 49, Issue 4, Page(s) 1136–1147

    Abstract: Purpose: To develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas.: Methods: Ga-68-Trivehexin was synthesized by trimerization of the optimized αvβ6-integrin selective cyclic nonapeptide Tyr2 (sequence: c[ ... ...

    Abstract Purpose: To develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas.
    Methods: Ga-68-Trivehexin was synthesized by trimerization of the optimized αvβ6-integrin selective cyclic nonapeptide Tyr2 (sequence: c[YRGDLAYp(NMe)K]) on the TRAP chelator core, followed by automated labeling with Ga-68. The tracer was characterized by ELISA for activities towards integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1, as well as by cell binding assays on H2009 (αvβ6-positive) and MDA-MB-231 (αvβ6-negative) cells. SCID-mice bearing subcutaneous xenografts of the same cell lines were used for dynamic (90 min) and static (75 min p.i.) µPET imaging, as well as for biodistribution (90 min p.i.). Structure-activity-relationships were established by comparison with the predecessor compound Ga-68-TRAP(AvB6)
    Results: Ga-68-Trivehexin showed a high αvβ6-integrin affinity (IC
    Conclusions: Ga-68-Trivehexin is a valuable probe for imaging of αvβ6-integrin expression in human cancers.
    MeSH term(s) Animals ; Cell Line, Tumor ; Gallium Radioisotopes ; Head and Neck Neoplasms ; Humans ; Integrin alphaVbeta3/metabolism ; Integrins/metabolism ; Mice ; Mice, SCID ; Pancreatic Neoplasms/diagnostic imaging ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography/methods ; Squamous Cell Carcinoma of Head and Neck ; Tissue Distribution ; Pancreatic Neoplasms
    Chemical Substances Gallium Radioisotopes ; Integrin alphaVbeta3 ; Integrins ; Gallium-68 (98B30EPP5S)
    Language English
    Publishing date 2021-09-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-021-05559-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  7. Article ; Online: Click-Chemistry (CuAAC) Trimerization of an α

    Quigley, Neil Gerard / Tomassi, Stefano / Di Leva, Francesco Saviero / Di Maro, Salvatore / Richter, Frauke / Steiger, Katja / Kossatz, Susanne / Marinelli, Luciana / Notni, Johannes

    Chembiochem : a European journal of chemical biology

    2020  Volume 21, Issue 19, Page(s) 2836–2843

    Abstract: ... ...

    Abstract α
    MeSH term(s) Adenocarcinoma of Lung/diagnostic imaging ; Animals ; Antigens, Neoplasm/analysis ; Aza Compounds/chemistry ; Click Chemistry ; Coordination Complexes/chemical synthesis ; Coordination Complexes/chemistry ; Female ; Gallium Radioisotopes ; Humans ; Integrins/analysis ; Lung Neoplasms/diagnostic imaging ; Mice ; Mice, SCID ; Molecular Structure ; Neoplasms, Experimental/diagnostic imaging ; Peptides, Cyclic/chemistry ; Phosphinic Acids/chemistry ; Piperidines/chemistry ; Positron-Emission Tomography ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/chemistry ; Tumor Cells, Cultured
    Chemical Substances Antigens, Neoplasm ; Aza Compounds ; Coordination Complexes ; Gallium Radioisotopes ; Integrins ; Peptides, Cyclic ; Phosphinic Acids ; Piperidines ; Radiopharmaceuticals ; integrin alphavbeta6 ; triazacyclononane ; Gallium-68 (98B30EPP5S)
    Language English
    Publishing date 2020-06-09
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202000200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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