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

Omer Aras, Cetin Demirdag, Harikrishna Kommidi, Hua Guo, Ina Pavlova, Aslan Aygun, Emre Karayel, Hüseyin Pehlivanoglu, Nami Yeyin, Natasha Kyprianou, Nandi Chen, Stefan Harmsen, Kerim Sonmezoglu, Dara J. Lundon, Rahmi Oklu, Richard Ting, Ashutosh Tewari, Oguz Akin, Haluk B. Sayman

Research output: Contribution to journalArticlepeer-review


Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)405-416
Number of pages12
JournalClinical Genitourinary Cancer
Issue number5
StatePublished - Oct 2021


  • Image-guided surgery
  • PET imaging
  • PSMA
  • Positron emission tomography
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology


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