First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment
Purpose: PGN650 is a F(ab′) 2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124 I to create a positron emission t...
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SAGE Publishing
2017-10-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012117733349 |
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| author | Richard Laforest PhD Farrokh Dehdashti MD Yongjian Liu PhD Jennifer Frye CMMT Sarah Frye CMMT Hannah Luehmann Deborah Sultan Joseph S. Shan PhD Bruce D. Freimark PhD Barry A. Siegel MD |
| author_facet | Richard Laforest PhD Farrokh Dehdashti MD Yongjian Liu PhD Jennifer Frye CMMT Sarah Frye CMMT Hannah Luehmann Deborah Sultan Joseph S. Shan PhD Bruce D. Freimark PhD Barry A. Siegel MD |
| author_sort | Richard Laforest PhD |
| collection | DOAJ |
| description | Purpose: PGN650 is a F(ab′) 2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124 I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. Methods: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124 I-PGN650 intravenously and underwent positron emission tomography–computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). Results: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. Conclusion: Although 124 I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies. |
| format | Article |
| id | doaj-art-002fdbd0231544628bd7770595a4e3e1 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2017-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-002fdbd0231544628bd7770595a4e3e12025-01-03T00:10:42ZengSAGE PublishingMolecular Imaging1536-01212017-10-011610.1177/1536012117733349First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor MicroenvironmentRichard Laforest PhD0Farrokh Dehdashti MD1Yongjian Liu PhD2Jennifer Frye CMMT3Sarah Frye CMMT4Hannah Luehmann5Deborah Sultan6Joseph S. Shan PhD7Bruce D. Freimark PhD8Barry A. Siegel MD9 Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA Peregrine Pharmaceuticals Inc, Tustin, CA, USA Peregrine Pharmaceuticals Inc, Tustin, CA, USA Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USAPurpose: PGN650 is a F(ab′) 2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124 I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. Methods: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124 I-PGN650 intravenously and underwent positron emission tomography–computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). Results: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. Conclusion: Although 124 I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies.https://doi.org/10.1177/1536012117733349 |
| spellingShingle | Richard Laforest PhD Farrokh Dehdashti MD Yongjian Liu PhD Jennifer Frye CMMT Sarah Frye CMMT Hannah Luehmann Deborah Sultan Joseph S. Shan PhD Bruce D. Freimark PhD Barry A. Siegel MD First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment Molecular Imaging |
| title | First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment |
| title_full | First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment |
| title_fullStr | First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment |
| title_full_unstemmed | First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment |
| title_short | First-in-Man Evaluation of I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment |
| title_sort | first in man evaluation of i pgn650 a pet tracer for detecting phosphatidylserine as a biomarker of the solid tumor microenvironment |
| url | https://doi.org/10.1177/1536012117733349 |
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