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Research ArticleClinical Investigation

Photoacoustic Molecular Imaging for the Identification of Lymph Node Metastasis in Head and Neck Cancer Using an Anti-EGFR Antibody–Dye Conjugate

Naoki Nishio, Nynke S. van den Berg, Brock A. Martin, Stan van Keulen, Shayan Fakurnejad, Eben L. Rosenthal and Katheryne E. Wilson
Journal of Nuclear Medicine May 2021, 62 (5) 648-655; DOI: https://doi.org/10.2967/jnumed.120.245241
Naoki Nishio
1Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, California
2Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
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Nynke S. van den Berg
1Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, California
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Brock A. Martin
3Department of Pathology, Stanford University School of Medicine, Stanford, California; and
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Stan van Keulen
1Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, California
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Shayan Fakurnejad
1Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, California
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Eben L. Rosenthal
1Department of Otolaryngology–Head and Neck Surgery, Stanford University School of Medicine, Stanford, California
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Katheryne E. Wilson
4Department of Radiology, Stanford University School of Medicine, Stanford, California
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  • FIGURE 1.
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    FIGURE 1.

    Workflow of photoacoustic and fluorescence imaging of pan800 in HNSCC and LNs, including intraoperative, postoperative, and histologic imaging. All scale bars are 5 mm. H&E = hematoxylin and eosin.

  • FIGURE 2.
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    FIGURE 2.

    Determining optical absorption spectra (A) and photoacoustic (B) and fluorescence (C) imaging sensitivity for pan800. deOxy hemo = deoxygenated hemoglobin; Oxy hemo = oxygenated hemoglobin.

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    FIGURE 3.

    Photoacoustic (A) and fluorescence (B) imaging of decreasing concentrations of pan800 in tissue-mimicking phantom. avg = average.

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    FIGURE 4.

    Fluorescence, spectroscopic photoacoustic pan800 signal, and histology images from representative patient with primary tumor and benign LNs. Tumor is outlined in red dashed line. White arrows represent locations of several LNs within neck specimen; red dashed circle highlights the LN shown by histology at the bottom right. All scale bars are 5 mm. H&E = hematoxylin and eosin; US = ultrasound.

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    FIGURE 5.

    Discrimination of metastatic LNs from benign LNs from head and neck cancer patients using fluorescence imaging. (A) Bright-field and fluorescence images of metastatic and benign LNs corresponding to hematoxylin-and-eosin slides. (B) Quantitative analysis of mean fluorescence intensity for differentiating benign from metastatic LNs. All scale bars are 5 mm. H&E = hematoxylin and eosin.

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    FIGURE 6.

    Photoacoustic measurements for metastatic and benign LNs. (A) Representative ultrasound, spectroscopic photoacoustic, fluorescence, and histology images of benign and metastatic LNs. Photoacoustic signals corresponding to pan800 and oxy- and deoxyhemoglobin have been spectrally unmixed. All scale bars are 5 mm. (B) Quantitative analysis of PAMI signal using pan800 avg. (C) Quantitative analysis of PAMI signal using pan800 avg thresh. US = ultrasound.

  • FIGURE 7.
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    FIGURE 7.

    Heterogeneity of pan800 in metastatic LNs. (A) Representative ultrasound, photoacoustic, fluorescence, and histology images of metastatic LN. All scale bars are 5 mm. (B) Quantitative and ROC analysis of ratio of PAMI signal using pan800 avg thresh to pan800 avg to differentiate benign from metastatic LNs. US = ultrasound.

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    TABLE 1

    Patient Characteristics

    Patient no.Age (y)SexTumor locationcTN stage
    170FemaleBuccal mucosaT3N0
    268FemaleLateral tongueT3N2b
    371FemaleLateral tongueT1N0
    447FemaleRetromolar trigoneT4N2b
    556MaleBuccal mucosaT2N0
    660MaleEarT2N0
    770MaleLateral tongueT3N0

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Journal of Nuclear Medicine: 62 (5)
Journal of Nuclear Medicine
Vol. 62, Issue 5
May 10, 2021
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Photoacoustic Molecular Imaging for the Identification of Lymph Node Metastasis in Head and Neck Cancer Using an Anti-EGFR Antibody–Dye Conjugate
Naoki Nishio, Nynke S. van den Berg, Brock A. Martin, Stan van Keulen, Shayan Fakurnejad, Eben L. Rosenthal, Katheryne E. Wilson
Journal of Nuclear Medicine May 2021, 62 (5) 648-655; DOI: 10.2967/jnumed.120.245241

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Photoacoustic Molecular Imaging for the Identification of Lymph Node Metastasis in Head and Neck Cancer Using an Anti-EGFR Antibody–Dye Conjugate
Naoki Nishio, Nynke S. van den Berg, Brock A. Martin, Stan van Keulen, Shayan Fakurnejad, Eben L. Rosenthal, Katheryne E. Wilson
Journal of Nuclear Medicine May 2021, 62 (5) 648-655; DOI: 10.2967/jnumed.120.245241
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Keywords

  • photoacoustic imaging
  • head and neck cancer
  • lymph node
  • antibody–dye
  • near-infrared
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