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Research ArticleClinical Investigation
Open Access

Imaging of Tumor Stroma Using 68Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial

Bingxin Gu, Ziyi Yang, Xinyue Du, Xiaoping Xu, Xiaomin Ou, Zuguang Xia, Qing Guan, Silong Hu, Zhongyi Yang and Shaoli Song
Journal of Nuclear Medicine March 2024, 65 (3) 365-371; DOI: https://doi.org/10.2967/jnumed.123.266556
Bingxin Gu
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;
3Center for Biomedical Imaging, Fudan University, Shanghai, China;
4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;
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Ziyi Yang
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;
3Center for Biomedical Imaging, Fudan University, Shanghai, China;
4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;
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Xinyue Du
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;
3Center for Biomedical Imaging, Fudan University, Shanghai, China;
4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;
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Xiaoping Xu
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;
3Center for Biomedical Imaging, Fudan University, Shanghai, China;
4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;
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Xiaomin Ou
5Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China;
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Zuguang Xia
6Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; and
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Qing Guan
7Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
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Silong Hu
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;
3Center for Biomedical Imaging, Fudan University, Shanghai, China;
4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;
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Zhongyi Yang
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;
3Center for Biomedical Imaging, Fudan University, Shanghai, China;
4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;
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Shaoli Song
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;
3Center for Biomedical Imaging, Fudan University, Shanghai, China;
4Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;
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  • FIGURE 1.
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    FIGURE 1.

    Box plots of SUVmax (A) and TLR (B) detected on 18F-FDG and 68Ga-FAPI PET/CT. Primary tumors showed significantly higher semiquantitative uptake of 68Ga-FAPI than 18F-FDG (P < 0.001). 18F-FDG outperformed 68Ga-FAPI PET/CT in detecting lymph node metastases, with significantly higher SUVmax (P < 0.001). In terms of TLR, lymph node and bone metastases presented more favorable uptake of 68Ga-FAPI than 18F-FDG (P < 0.001). ***P < 0.001. NS = no significance.

  • FIGURE 2.
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    FIGURE 2.

    PET/CT and MR images of 72-y-old woman (patient 30) pathologically confirmed with metastatic squamous cell carcinoma of right neck. (A) 18F-FDG PET images (left and top) and PET/CT images (bottom), shown in coronal, sagittal, and axial views (from left to right), demonstrated metastatic lymph node of right neck with intensive metabolic activity (black arrow, SUVmax, 30.1) but presented no evidence for primary tumor. (B) 68Ga-FAPI PET images (top and right) and PET/CT images (bottom), shown in axial, sagittal, and coronal views (from left to right), also detected metastatic lymph node with high 68Ga-FAPI activity (black arrow, SUVmax, 16.3). There was intensive uptake of 68Ga-FAPI in palate (red arrow, SUVmax, 11.3). (C) T1-weighted, T2-weighted, and contrast-enhanced T1-weighted MRI also presented no evidence for primary tumor. Subsequent surgery confirmed mucoepidermoid carcinoma of palate. C+ = contrast-enhanced.

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    FIGURE 3.

    Kaplan–Meier curve for progression-free survival (PFS). HR = hazard rate.

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    TABLE 1.

    Baseline Characteristics

    CharacteristicTotal, n = 91Primary tumor identified, n = 46Primary tumor unidentified, n = 45P
    Sex0.793
     Female18 (20)10 (22)8 (18)
     Male73 (80)36 (78)37 (82)
    Age (y)60 (24–76)55 (33–76)61 (24–73)0.238
    Body mass index (kg/m2)23 (10–31)23 (10–29)24 (18–31)0.149
    Pathologic type of cervical lymph node0.198
     Squamous cell carcinoma81 (89)42 (91)39 (86)
     Adenocarcinoma7 (8)4 (9)3 (7)
     Poorly differentiated carcinoma3 (3)0 (0)3 (7)
    EBV DNA status0.024*
     Positive16 (17)13 (28)3 (7)
     Negative47 (52)20 (44)27 (60)
     Unknown28 (31)13 (28)15 (33)
    Human papillomavirus status0.787
     Positive10 (11)6 (13)4 (9)
     Negative11 (12)5 (11)6 (13)
     Unknown70 (77)35 (76)35 (78)
    EBV-encoded RNA status0.028*
     Positive18 (20)13 (28)5 (11)
     Negative39 (43)14 (31)25 (56)
     Unknown34 (37)19 (41)15 (33)
    p16 status0.405
     Positive20 (22)12 (26)8 (18)
     Negative27 (30)11 (24)16 (35)
     Unknown44 (48)23 (50)21 (47)
    Surgery0.677
     Yes45 (49)24 (52)21 (47)
     No46 (51)22 (48)24 (53)
    Chemotherapy0.026*
     Yes70 (77)40 (87)30 (67)
     No21 (23)6 (13)15 (33)
    Radiotherapy<0.001*
     Yes54 (59)37 (80)17 (38)
     No37 (41)9 (20)28 (62)
    Targeted therapy0.231
     Yes12 (13)4 (9)8 (18)
     No79 (87)42 (91)37 (82)
    Immunotherapy0.714
     Yes8 (9)5 (11)3 (7)
     No83 (91)41 (89)42 (93)
    Progression-free survival0.014*
     Progression12 (13)2 (4)10 (22)
     Progression-free79 (87)44 (96)35 (78)
    Follow-up (mo)19 (7–33)18 (7–32)19 (7–33)0.708
    • ↵* Statistically significant at P < 0.05.

    • EBV = Epstein–Barr virus.

    • Qualitative data are number and percentage; continuous data are median or mean and range.

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    TABLE 2.

    Comparison of Primary Tumors Detected on 18F-FDG and 68Ga-FAPI PET/CT

    Primary tumor siteTotal (n)18F-FDG68Ga-FAPITreatment change led by 68Ga-FAPI
    Nasopharynx14 (4)614 (4)4
    Tonsil21 (3)521 (3)13
    Palatine tonsil13 (2)313 (2)8
    Lingual tonsil8 (1)28 (1)5
    Submandibular gland3132
    Thyroid3330
    Hypopharynx2022
    Tongue1110
    Laryngopharynx1110
    Palate1011
    Total, n = 9146 (51%)17 (19%)46 (51%)22 (24%)
    • Primary tumor site data in parentheses indicate primary tumor was pathologically negative but diagnosed clinically. Total tumor data are number and percentage (P < 0.001).

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    TABLE 3.

    Diagnostic Performance of Contrast-Enhanced CT, Contrast-Enhanced MRI, 18F-FDG, and 68Ga-FAPI PET/CT in Identifying Primary Tumors

    Test characteristicContrast-enhanced CTContrast-enhanced MRI18F-FDG68Ga-FAPI
    True-positive (n)12151746
    False-positive (n)1521231
    False-negative (n)60405144
    Sensitivity (%)17272551
    Positive predictive value (%)44424398
    Accuracy rate (%)14201951

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Journal of Nuclear Medicine: 65 (3)
Journal of Nuclear Medicine
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March 1, 2024
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Imaging of Tumor Stroma Using 68Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial
Bingxin Gu, Ziyi Yang, Xinyue Du, Xiaoping Xu, Xiaomin Ou, Zuguang Xia, Qing Guan, Silong Hu, Zhongyi Yang, Shaoli Song
Journal of Nuclear Medicine Mar 2024, 65 (3) 365-371; DOI: 10.2967/jnumed.123.266556

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Imaging of Tumor Stroma Using 68Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial
Bingxin Gu, Ziyi Yang, Xinyue Du, Xiaoping Xu, Xiaomin Ou, Zuguang Xia, Qing Guan, Silong Hu, Zhongyi Yang, Shaoli Song
Journal of Nuclear Medicine Mar 2024, 65 (3) 365-371; DOI: 10.2967/jnumed.123.266556
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Keywords

  • fibroblast activation protein
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