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. Author manuscript; available in PMC: 2022 Oct 1.
Published in final edited form as: Eur J Nucl Med Mol Imaging. 2021 Apr 16;48(11):3732–3733. doi: 10.1007/s00259-021-05344-w

Simultaneous Injection of 18F-BF3 Cy3-ACUPA and Non-Radioactive Cy7-ACUPA Probes: A Promising Pre-Biopsy PET and Ex-Vivo Fluorescence Imaging Approach to Evaluate Prostate Cancer

Omer Aras 1,*, Cetin Demirdag 2, Harikrishna Kommidi 3, Ina Pavlova 4, Vitaly Boyko 5, Dara J Lundon 4, Richard Ting 2, Ashutosh Tewari 4, Oguz Akin 1, Haluk B Sayman 6
PMCID: PMC8440416  NIHMSID: NIHMS1727410  PMID: 33860854

Positron emission tomography (PET) with radiolabelled ligands having high affinity to prostate membrane-specific membrane antigen (PSMA) is promising for the evaluation of prostate cancer (PCa) [1–3]. Hybrid PET/ fluorescent probes could offer synergistic benefits over a single modality approach through pre-biopsy tumor detection by radioactivity and post biopsy tumor confirmation by fluorescence and facilitate fluorescence-guided surgery. Here, we report for the first-time prebiopsy PET/MR imaging and subsequent ex-vivo dual fluorescence imaging of PSMA positive PCa. A 74-year-old man with a PSA level of 8 ng/mL (3 ng/mL a year ago) underwent a prebiopsy 68Ga PSMA PET/CT. Two weeks later, 18F-BF3-Cy3-ACUPA PET imaging matched with 68Ga-PSMA imaging were performed. Both 3D MIP 68Ga-PSMA (a) and 18F-BF3-Cy3-ACUPA (b) PET/MRI images showed increased uptake in the right peripheral zone mid gland to apex (a, PSMA+ cancer indicated with arrows; c–f with dotted rectangle). Fusion biopsy one week after the injection confirmed Gleason 8 (4+4) PCa. Ex-vivo fluorescence microscopy of the targeted biopsy showed Cy3 (g and j, red signal) and Cy7 (h and k, green signal) ACUPA targeting PSMA-positive tumor foci with high rate of overlap indicating high tumor-specific bindings of both probes (fused Cy3 and Cy7, i and l; and 3D MIP fused, m).

Given known differences in tissue penetration (surface for Cy3-visible fluorescence vs deeper for Cy7-near infrared fluorescence) of the cyanine dyes, the presented case revealed similar fluorescence kinetics in-vivo and specific targeting to PSMA which can provide an additional advantage of this approach in fluorescence-guided surgery. Our initial experience with hybrid modality imaging agent demonstrates its potential in precisely detecting PSMA-expressing tumors pre-biopsy and after biopsy which could provide both PET and fluorescence imaging guidance for PCa.

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Funding:

Omer Aras and Oguz Akin were partially funded by NIH/NCI Cancer Center Support Grant P30 CA008748.

Footnotes

Publisher's Disclaimer: This Author Accepted Manuscript is a PDF file of a an unedited peer-reviewed manuscript that has been accepted for publication but has not been copyedited or corrected. The official version of record that is published in the journal is kept up to date and so may therefore differ from this version.

Conflict of Interest: Richard Ting and Omer Aras are minor stakeholders in Trace Imaging Technologies. The other authors declare that they have no conflict of interest.

Informed consent: The patient was enrolled in and provided informed consent for a clinical trial of 18F-BF3-Cy3-ACUPA or non-radioactive Cy3-ACUPA and 68Ga-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI) approved by the institutional review board at Cerrahpasa University School of Medicine (protocol #-29281604.01.01-139206). Informed consent was obtained from the participant included in the study.

References:

  • 1.Johnson DC, Raman SS, Mirak SA, Kwan L, Bajgiran AM, Hsu W, Maehara CK, Ahuja P, Faiena I, Pooli A, Salmasi A, Sisk A, Felker ER, Lu DSK, Reiter RE. Detection of Individual Prostate Cancer Foci via Multiparametric Magnetic Resonance Imaging. Eur Urol. 2019;75(5):712–720. [DOI] [PubMed] [Google Scholar]
  • 2.Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous (68)Ga-PSMA HBED-CC PET/MRI Improves the Localization of Primary Prostate Cancer. Eur Urol. 2016;70(5):829–36 [DOI] [PubMed] [Google Scholar]
  • 3.Bettermann AS, Zamboglou C, Kiefer S, Jilg CA, Spohn S, Kranz-Rudolph J, et al. [(68)Ga-]PSMA-11 PET/CT and multiparametric MRI for gross tumor volume delineation in a slice by slice analysis with whole mount histopathology as a reference standard - Implications for focal radiotherapy planning in primary prostate cancer. Radiother Oncol. 2019;141:214–9. [DOI] [PubMed] [Google Scholar]
  • 4.Kommidi H, Guo H, Nurili F, Vedvyas Y, Jin MM, McClure TD, Ehdaie B, Sayman HB, Akin O, Aras O, Ting R. 18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management. J Med Chem. 2018;61:4256–4262. [DOI] [PMC free article] [PubMed] [Google Scholar]

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