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  1. AU="Lofland, Gabriela"
  2. AU="Zou, Xiaoyan"
  3. AU="Norhafizah Bt Sahril"

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  1. Article ; Online: CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.

    Sharma, Ajay Kumar / Gupta, Kuldeep / Mishra, Akhilesh / Lofland, Gabriela / Marsh, Ian / Kumar, Dhiraj / Ghiaur, Gabriel / Imus, Philip / Rowe, Steven P / Hobbs, Robert F / Gocke, Christian B / Nimmagadda, Sridhar

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2024  Volume 11, Issue 16, Page(s) e2308617

    Abstract: The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, a first-in-class peptide-based radiotracer, [ ...

    Abstract The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, a first-in-class peptide-based radiotracer, [
    MeSH term(s) Gallium Radioisotopes ; Multiple Myeloma/drug therapy ; Multiple Myeloma/metabolism ; Multiple Myeloma/diagnostic imaging ; Animals ; ADP-ribosyl Cyclase 1/metabolism ; Mice ; Humans ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/pharmacokinetics ; Disease Models, Animal ; Peptides/metabolism ; Membrane Glycoproteins/metabolism ; Cell Line, Tumor
    Chemical Substances Gallium Radioisotopes ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6) ; Gallium-68 (98B30EPP5S) ; Radiopharmaceuticals ; Peptides ; CD38 protein, human (EC 3.2.2.5) ; Membrane Glycoproteins
    Language English
    Publishing date 2024-02-29
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202308617
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Preclinical Evaluation of a New Series of Albumin-Binding

    Boinapally, Srikanth / Alati, Suresh / Jiang, Zirui / Yan, Yu / Lisok, Alla / Singh, Rajan / Lofland, Gabriela / Minn, Il / Hobbs, Robert F / Pomper, Martin G / Banerjee, Sangeeta Ray

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 16

    Abstract: Prostate-specific membrane antigen (PSMA)-based low-molecular-weight agents using beta(β)-particle-emitting radiopharmaceuticals is a new treatment paradigm for patients with metastatic castration-resistant prostate cancer. Although results have been ... ...

    Abstract Prostate-specific membrane antigen (PSMA)-based low-molecular-weight agents using beta(β)-particle-emitting radiopharmaceuticals is a new treatment paradigm for patients with metastatic castration-resistant prostate cancer. Although results have been encouraging, there is a need to improve the tumor residence time of current PSMA-based radiotherapeutics. Albumin-binding moieties have been used strategically to enhance the tumor uptake and retention of existing PSMA-based investigational agents. Previously, we developed a series of PSMA-based, β-particle-emitting, low-molecular-weight compounds. From this series,
    MeSH term(s) Humans ; Male ; Animals ; Mice ; Ligands ; Tissue Distribution ; Albumins ; Beta Particles ; Butyric Acid
    Chemical Substances Ligands ; Albumins ; Butyric Acid (107-92-6)
    Language English
    Publishing date 2023-08-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28166158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  3. Article ; Online: Non-invasive PD-L1 quantification using [

    Mishra, Akhilesh / Gupta, Kuldeep / Kumar, Dhiraj / Lofland, Gabriela / Sharma, Ajay Kumar / Solnes, Lilja B / Rowe, Steven P / Forde, Patrick M / Pomper, Martin G / Gabrielson, Edward W / Nimmagadda, Sridhar

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 10

    Abstract: Background: Combination therapies that aim to improve the clinical efficacy to immune checkpoint inhibitors have led to the need for non-invasive and early pharmacodynamic biomarkers. Positron emission tomography (PET) is a promising non-invasive ... ...

    Abstract Background: Combination therapies that aim to improve the clinical efficacy to immune checkpoint inhibitors have led to the need for non-invasive and early pharmacodynamic biomarkers. Positron emission tomography (PET) is a promising non-invasive approach to monitoring target dynamics, and programmed death-ligand 1 (PD-L1) expression is a central component in cancer immunotherapy strategies. [
    Methods: Cell lines and xenografts derived from three non-small cell lung cancers (NSCLCs) and three urothelial carcinomas (UCs) were used to validate the specificity of [
    Results: [
    Conclusion: [
    MeSH term(s) Humans ; Animals ; Mice ; B7-H1 Antigen ; Tissue Distribution ; Carcinoma, Non-Small-Cell Lung ; Positron-Emission Tomography/methods ; Immunotherapy/methods ; Lung Neoplasms
    Chemical Substances CD274 protein, human ; B7-H1 Antigen
    Language English
    Publishing date 2023-10-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-007535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A Gallium-68-Labeled Peptide Radiotracer For CD38-Targeted Imaging In Multiple Myeloma With PET.

    Sharma, Ajay Kumar / Gupta, Kuldeep / Mishra, Akhilesh / Lofland, Gabriela / Marsh, Ian / Kumar, Dhiraj / Ghiaur, Gabriel / Imus, Philip / Hobbs, Robert F / Gocke, Christian B / Nimmagadda, Sridhar

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Purpose: The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, we developed [68Ga]Ga-AJ206, a peptide- ... ...

    Abstract Purpose: The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, we developed [68Ga]Ga-AJ206, a peptide-based radiotracer that can be seamlessly integrated into the standard clinical workflow and is specifically designed to non-invasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET).
    Experimental design: We synthesized a high-affinity binder for quantification of CD38 levels. Affinity was tested using surface plasmon resonance, and In vitro specificity was evaluated using a gallium-68-labeled analog. Distribution, pharmacokinetics, and CD38 specificity of the radiotracer were assessed in MM cell lines and in primary patient-derived myeloma cells and xenografts (PDX) with cross-validation by flow cytometry and immunohistochemistry. Furthermore, we investigated the radiotracer's potential to quantify CD38 pharmacodynamics induced by all-trans retinoic acid therapy (ATRA).
    Results: [68Ga]Ga-AJ206 exhibited high CD38 binding specificity (KD: 19.1±0.99 nM) and CD38-dependent In vitro binding. [68Ga]Ga-AJ206-PET showed high contrast within 60 minutes and suitable absorbed dose estimates for clinical use. Additionally, [68Ga]Ga-AJ206 detected CD38 expression in xenografts, PDXs and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [68Ga]Ga-AJ206-PET successfully quantified CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following ATRA therapy.
    Conclusions: [68Ga]Ga-AJ206 exhibited the salient features required for clinical translation, providing CD38-specific high contrast images in multiple models of MM. [68Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.09.540036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Gallium-68-labeled Peptide PET Quantifies Tumor Exposure of PD-L1 Therapeutics.

    Mishra, Akhilesh / Kumar, Dhiraj / Gupta, Kuldeep / Lofland, Gabriela / Sharma, Ajay Kumar / Banka, Dhanush S / Hobbs, Robert F / Dannals, Robert F / Rowe, Steven P / Gabrielson, Edward / Nimmagadda, Sridhar

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2022  Volume 29, Issue 3, Page(s) 581–591

    Abstract: Purpose: Immune checkpoint therapy (ICT) is currently ineffective in a majority of patients. Tumor drug exposure measurements can provide vital insights into mechanisms involved in the resistance of solid tumors to those therapeutics; however, tools to ... ...

    Abstract Purpose: Immune checkpoint therapy (ICT) is currently ineffective in a majority of patients. Tumor drug exposure measurements can provide vital insights into mechanisms involved in the resistance of solid tumors to those therapeutics; however, tools to quantify in situ drug exposure are few. We have investigated the potential of programmed death-ligand 1 (PD-L1) pharmacodynamics, quantified using PET, to inform on the tumor exposure of anti-PD-L1 (aPD-L1) therapeutics.
    Experimental design: To noninvasively quantify PD-L1 levels, we first developed a novel peptide-based gallium-68-labeled binder, [68Ga]Ga-DK223, and evaluated its in vivo distribution, pharmacokinetics, and PD-L1 specificity in preclinical models of triple-negative breast cancer and urothelial carcinoma with variable PD-L1 expression. We then quantified baseline and accessible PD-L1 levels in tumors as a noninvasive pharmacodynamic measure to assess tumor exposure to two aPD-L1 antibodies (avelumab and durvalumab).
    Results: DK223 exhibited a KD of 1.01±0.83 nmol/L for PD-L1 and inhibited the PD-1:PD-L1 interaction in a dose-dependent manner. [68Ga]Ga-DK223 provides high-contrast PET images within 60 minutes of administration and detects PD-L1 in an expression-dependent manner in xenograft models. PD-L1 pharmacodynamics measured using [68Ga]Ga-DK223-PET revealed that avelumab and durvalumab had similar exposure early during therapy, but only durvalumab exhibited sustained exposure at the tumor.
    Conclusions: [68Ga]Ga-DK223 detected variable PD-L1 levels and exhibited salient features required for clinical translation. [68Ga]Ga-DK223-PET could be useful for quantifying total PD-L1 levels at baseline and accessible PD-L1 levels during therapy to understand drug exposure at the tumor, thus supporting its use for guiding and optimizing ICT.
    MeSH term(s) Humans ; Carcinoma, Transitional Cell ; Positron-Emission Tomography/methods ; Urinary Bladder Neoplasms ; B7-H1 Antigen/metabolism ; Peptides
    Chemical Substances Gallium-68 (98B30EPP5S) ; CD274 protein, human ; B7-H1 Antigen ; Peptides
    Language English
    Publishing date 2022-11-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-22-1931
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Hetero-bivalent agents targeting FAP and PSMA.

    Boinapally, Srikanth / Lisok, Alla / Lofland, Gabriela / Minn, Il / Yan, Yu / Jiang, Zirui / Shin, Min Jay / Merino, Vanessa F / Zheng, Lei / Brayton, Cory / Pomper, Martin G / Banerjee, Sangeeta Ray

    European journal of nuclear medicine and molecular imaging

    2022  Volume 49, Issue 13, Page(s) 4369–4381

    Abstract: Purpose: We developed a theranostic radiopharmaceutical that engages two key cell surface proteases, fibroblast activation protein alpha (FAP) and prostate-specific membrane antigen (PSMA), each frequently overexpressed within the tumor microenvironment ...

    Abstract Purpose: We developed a theranostic radiopharmaceutical that engages two key cell surface proteases, fibroblast activation protein alpha (FAP) and prostate-specific membrane antigen (PSMA), each frequently overexpressed within the tumor microenvironment (TME). The latter is also expressed in most prostate tumor epithelium. To engage a broader spectrum of cancers for imaging and therapy, we conjugated small-molecule FAP and PSMA-targeting moieties using an optimized linker to provide <sup>64</sup>Cu-labeled compounds.
    Methods: We synthesized FP-L1 and FP-L2 using two linker constructs attaching the FAP and PSMA-binding pharmacophores. We determined in vitro inhibition constants (K<sub>i</sub>) for FAP and PSMA. Cell uptake assays and flow cytometry were conducted in human glioma (U87), melanoma (SK-MEL-24), prostate cancer (PSMA + PC3 PIP and PSMA - PC3 flu), and clear cell renal cell carcinoma lines (PSMA + /PSMA - 786-O). Quantitative positron emission tomography/computed tomography (PET/CT) and tissue biodistribution studies were performed using U87, SK-MEL-24, PSMA + PC3 PIP, and PSMA + 786-O experimental xenograft models and the KPC genetically engineered mouse model of pancreatic cancer.
    Results: <sup>64</sup>Cu-FP-L1 and <sup>64</sup>Cu-FP-L2 were produced in high radiochemical yields (> 98%) and molar activities (> 19 MBq/nmol). K<sub>i</sub> values were in the nanomolar range for both FAP and PSMA. PET imaging and biodistribution studies revealed high and specific targeting of <sup>64</sup>Cu-FP-L1 and <sup>64</sup>Cu-FP-L2 for FAP and PSMA. <sup>64</sup>Cu-FP-L1 displayed more favorable pharmacokinetics than <sup>64</sup>Cu-FP-L2. In the U87 tumor model at 2 h post-injection, tumor uptake of <sup>64</sup>Cu-FP-L1 (10.83 ± 1.02%ID/g) was comparable to <sup>64</sup>Cu-FAPI-04 (9.53 ± 2.55%ID/g). <sup>64</sup>Cu-FP-L1 demonstrated high retention 5.34 ± 0.29%ID/g at 48 h in U87 tumor. Additionally, <sup>64</sup>Cu-FP-L1 showed high retention in PSMA + PC3 PIP tumor (12.06 ± 0.78%ID/g at 2 h and 10.51 ± 1.82%ID/g at 24 h).
    Conclusions: <sup>64</sup>Cu-FP-L1 demonstrated high and specific tumor targeting of FAP and PSMA. This compound should enable imaging of lesions expressing FAP, PSMA, or both on the tumor cell surface or within the TME. FP-L1 can readily be converted into a theranostic for the management of heterogeneous tumors.
    MeSH term(s) Animals ; Male ; Mice ; Humans ; Radiopharmaceuticals/pharmacokinetics ; Positron Emission Tomography Computed Tomography/methods ; Tissue Distribution ; Cell Line, Tumor ; Glutamate Carboxypeptidase II/metabolism ; Positron-Emission Tomography ; Prostatic Neoplasms/pathology ; Tumor Microenvironment
    Chemical Substances Radiopharmaceuticals ; Glutamate Carboxypeptidase II (EC 3.4.17.21)
    Language English
    Publishing date 2022-08-15
    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/s00259-022-05933-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1227: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Correction to: Hetero-bivalent agents targeting FAP and PSMA.

    Boinapally, Srikanth / Lisok, Alla / Lofland, Gabriela / Minn, Il / Yan, Yu / Jiang, Zirui / Shin, Min Jay / Merino, Vanessa F / Zheng, Lei / Brayton, Cory / Pomper, Martin G / Banerjee, Sangeeta Ray

    European journal of nuclear medicine and molecular imaging

    2022  Volume 49, Issue 13, Page(s) 4755

    Language English
    Publishing date 2022-08-31
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 8236-3
    ISSN 1619-7089 ; 0340-6997 ; 1619-7070
    ISSN (online) 1619-7089
    ISSN 0340-6997 ; 1619-7070
    DOI 10.1007/s00259-022-05951-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1227: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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