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Small Molecule, Multimodal, [18F]-PET and Fluorescence Imaging Agent Targeting Prostate-Specific Membrane Antigen: First-in-Human Study.

Authors
  • Aras, Omer1
  • Demirdag, Cetin2
  • Kommidi, Harikrishna3
  • Guo, Hua4
  • Pavlova, Ina5
  • Aygun, Aslan6
  • Karayel, Emre6
  • Pehlivanoglu, Hüseyin6
  • Yeyin, Nami6
  • Kyprianou, Natasha5
  • Chen, Nandi7
  • Harmsen, Stefan8
  • Sonmezoglu, Kerim6
  • Lundon, Dara J5
  • Oklu, Rahmi9
  • Ting, Richard3
  • Tewari, Ashutosh5
  • Akin, Oguz10
  • Sayman, Haluk B6
  • 1 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: [email protected]
  • 2 Department of Urology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey. , (Turkey)
  • 3 Department of Radiology, Molecular Imaging Innovations Institute (MI3), Weill Cornell Medicine, New York, NY, USA.
  • 4 Department of Radiology, Molecular Imaging Innovations Institute (MI3), Weill Cornell Medicine, New York, NY, USA; Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China; Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China. , (China)
  • 5 Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 6 Department of Nuclear Medicine, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey. , (Turkey)
  • 7 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Gastrointestinal Surgery, The Second Clinical Medicine College (Shenzhen People's Hospital) of Jinan University, Shenzhen, Guangdong, China. , (China)
  • 8 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 9 Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ, USA.
  • 10 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Type
Published Article
Journal
Clinical Genitourinary Cancer
Publisher
Elsevier
Publication Date
Oct 01, 2021
Volume
19
Issue
5
Pages
405–416
Identifiers
DOI: 10.1016/j.clgc.2021.03.011
PMID: 33879400
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A first-in-human study of [18F]-BF3-Cy3-ACUPA, a small-molecule imaging agent that can be unimolecularly both positron emitting and fluorescent, is conducted to determine its safety, biodistribution, radiation dosimetry, feasibility in tumor detection by preoperative positron emission tomography (PET), as well as its intraoperative fluorescence imaging utility in patients with prostate-specific membrane antigen positive (PSMA+) tumors. Ten patients aged 66 ± 7 years received a 6.5 ± 3.2 mCi intravenous injection of [18F]-BF3-Cy3-ACUPA and underwent PET/computed tomography (CT) imaging. Radiation dosimetry of [18F]-BF3-Cy3-ACUPA, normal organ biodistribution, and tumor uptakes were examined. Two patients were prescheduled for radical prostatectomy (RP) with extended pelvic lymphadenectomy approximately 24 hours following [18F]-BF3-Cy3-ACUPA injection and imaging. Without reinjection, intraoperative fluorescence imaging was performed on freshly excised tissue during RP. Frozen sections of excised tissue during RP were submitted for confirmatory histopathology and multiphoton fluorescence and brightfield microscopy. Absorbed doses by organs including the kidneys and salivary glands were similar to 68Ga-PSMA-11 imaging. [18F]-BF3-Cy3-ACUPA physiologic radiotracer accumulation and urinary/biliary excretion closely resembled the distribution of other published PSMA tracers including [18F]-JK-PSMA-7, [18F]-PSMA-1007, [18F]-DCFPyL, and [18F]-DCFBC. 19F-BF3-Cy3-ACUPA was retained in PSMA+ cancer tissues in patients for at least 24 hours, allowing for intraoperative fluorescence assessment of the prostate and of the embedded prostate cancer without contrast reinjection. After 24 hours, the imaging agent mostly decayed or cleared from the blood pool. Preoperative PET and fluorescence imaging findings were confirmed with final histopathology and multiphoton microscopy. Our first-in-human results demonstrate that [18F]-BF3-Cy3-ACUPA is safe and feasible in humans. Larger trials with this PET tracer are expected to further define its capabilities and its clinical role in the management of PSMA+ tumors, especially in prostate cancer. Copyright © 2021. Published by Elsevier Inc.

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