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OtherTheranostics

c-MET receptor-targeted fluorescence on the road to image-guided surgery in penile squamous cell carcinoma patients

Hielke Martijn de Vries, Elise Bekers, Matthias N van Oosterom, M Baris Krakullukcu, Henk G van der Poel, Fijs W.B. van Leeuwen, Tessa Buckle and Oscar Roberto Brouwer
Journal of Nuclear Medicine May 2021, jnumed.120.261864; DOI: https://doi.org/10.2967/jnumed.120.261864
Hielke Martijn de Vries
1 Netherlands Cancer Institute, Netherlands;
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Elise Bekers
1 Netherlands Cancer Institute, Netherlands;
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Matthias N van Oosterom -
2 Leiden University Medical Center, Netherlands;
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M Baris Krakullukcu
1 Netherlands Cancer Institute, Netherlands;
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Henk G van der Poel
1 Netherlands Cancer Institute, Netherlands;
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Fijs W.B. van Leeuwen
3 Leiden University Medical Centre;
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Tessa Buckle
2 Leiden University Medical Center, Netherlands;
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Oscar Roberto Brouwer
4 the Netherlands Cancer Institute, Netherlands
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Abstract

In penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could potentially improve margin detection and reduce unnecessary excision of healthy tissue. Here, we present the first results of a prospective feasibility study for real-time intraoperative visualization of pSCC using a fluorescent mesenchymal–epithelial transition factor (c-MET) receptor targeting tracer (EMI-137). Methods: EMI-137 tracer performance was initially assessed ex vivo (N = 10) via incubation of freshly excised pSCC in a solution containing EMI-137 (500 nM). The in vivo potential of c-MET targeting and intraoperative tumour visualization was assessed after intravenous administration of EMI-137 in five pSCC patients scheduled for surgical resection using a Cyanine-5 (Cy5) fluorescence camera. Fluorescence imaging results were related to standard pathological tumour evaluation and c-MET immunohistochemistry. Three of the five in vivo patients also underwent a sentinel node resection after local administration of the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. Results: No tracer-related adverse events were encountered. Both ex vivo and in vivo, EMI-137 enabled c-MET based tumour visualization in all patients. Histopathological analyses showed that all pSCC's expressed c-MET, with expression levels of ≥70% in 14/15 patients. Moreover, the highest c-MET expression levels were seen on the outside rim of the tumours, and a visual correlation was found between c-MET expression and fluorescence signal intensity. No complications were encountered when combining primary tumour targeting with lymphatic mapping. As such, simultaneous use of Cy5 and ICG in the same patient proved to be feasible. Conclusion: Fluorescence imaging of c-MET receptor-expressing pSCC tumours after intravenous injection of EMI-137 was shown to be feasible and can be combined with fluorescence-based lymphatic mapping. This combination is unique and paves the way towards further development of this surgical guidance approach.

  • Genitourinary
  • Molecular Imaging
  • Oncology: GU
  • Penile squamous cell carcinoma
  • c-MET receptor
  • fluorescence-guided surgery
  • multicolor
  • sentinel node
  • Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
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Journal of Nuclear Medicine: 63 (5)
Journal of Nuclear Medicine
Vol. 63, Issue 5
May 1, 2022
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c-MET receptor-targeted fluorescence on the road to image-guided surgery in penile squamous cell carcinoma patients
Hielke Martijn de Vries, Elise Bekers, Matthias N van Oosterom, M Baris Krakullukcu, Henk G van der Poel, Fijs W.B. van Leeuwen, Tessa Buckle, Oscar Roberto Brouwer
Journal of Nuclear Medicine May 2021, jnumed.120.261864; DOI: 10.2967/jnumed.120.261864

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c-MET receptor-targeted fluorescence on the road to image-guided surgery in penile squamous cell carcinoma patients
Hielke Martijn de Vries, Elise Bekers, Matthias N van Oosterom, M Baris Krakullukcu, Henk G van der Poel, Fijs W.B. van Leeuwen, Tessa Buckle, Oscar Roberto Brouwer
Journal of Nuclear Medicine May 2021, jnumed.120.261864; DOI: 10.2967/jnumed.120.261864
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Keywords

  • Genitourinary
  • molecular imaging
  • Oncology: GU
  • penile squamous cell carcinoma
  • c-MET receptor
  • fluorescence-guided surgery
  • multicolor
  • sentinel node
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