Research ArticleClinical Investigation
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Superior Tumor Detection for 68Ga-FAPI-46 Versus 18F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Kim M. Pabst, Marija Trajkovic-Arsic, Phyllis F.Y. Cheung, Simone Ballke, Katja Steiger, Timo Bartel, Benedikt M. Schaarschmidt, Aleksandar Milosevic, Robert Seifert, Michael Nader, Lukas Kessler, Jens T. Siveke, Katharina Lueckerath, Stefan Kasper, Ken Herrmann, Nader Hirmas, Hartmut H. Schmidt, Rainer Hamacher and Wolfgang P. Fendler
Journal of Nuclear Medicine July 2023, 64 (7) 1049-1055; DOI: https://doi.org/10.2967/jnumed.122.265215

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Enrollment flowchart. PDAC = pancreatic ductal adenocarcinoma; Q = questionnaire.

  • FIGURE 2.
    FIGURE 2.

    Maximum-intensity projections of 68Ga-FAPI-46 and 18F-FDG PET for all patients. Tumor lesions that could not be detected by 18F-FDG PET are marked with arrows. Tumor sites are listed in Table 2. N.A. = not applicable.

  • FIGURE 3.
    FIGURE 3.

    Lesion-based comparison of SUVmax between 68Ga-FAPI-46 and 18F-FDG PET/CT for lesion location (primary tumor, lymph node, distant metastases) (A), tumor grade (B), and location of primary tumor (C). *Statistically significant (P < 0.05). eCC = extrahepatic cholangiocarcinoma; G2 = grade 2; G3 = grade 3; iCC = intrahepatic cholangiocarcinoma; M = distant metastases; N = lymph nodes; ns = not statistically significant; T = primary tumor.

  • FIGURE 4.
    FIGURE 4.

    Intrahepatic primary tumor of patient 4, demonstrating 18.7-fold higher tumor-to-background uptake ratio in 68Ga-FAPI-46 PET (31.8) than in 18F-FDG PET (1.7).

  • FIGURE 5.
    FIGURE 5.

    Lesion-based comparison of TBR (blood pool, liver pool, left gluteal muscle; mean ± SD) between 68Ga-FAPI-46 and 18F-FDG PET for primary tumor (A), lymph node metastases (B), and distant metastases (C). Statistical significance is marked in black for 68Ga-FAPI-46 and in gray for 18F-FDG. *Statistically significant (P < 0.05). ns = not statistically significant.

  • FIGURE 6.
    FIGURE 6.

    Immunohistochemical FAP/GLUT1 expression graded in accordance with Table 1. (A). Histologic evaluation of tumor cell and stromal content in analyzed samples (2–5 samples per patient, 1 dot presents 1 patient, line presents mean value); tumor cell and stromal content were mostly comparable (∼50%). (B) On average, 90% of stromal cells are positive for FAP whereas 80% of cancer cells are positive for GLUT1. Line presents mean value. (C) Violin plots showing median intensity of 3 for FAP staining on stromal cells but 2 for GLUT1 staining on cancer cells. Line presents mean value. (D) Representative images of immunohistochemistry for FAP and GLUT1 on consecutive sections of 1 patient sample. FAP was strongly expressed in stroma, whereas GLUT1 was detected on tumor cells.

Tables

  • TABLE 1.

    Visual FAP/GLUT1 Grading

    GradeDefinition
    0Absence of FAP/GLUT1 positivity
    1Slight FAP/GLUT1 positivity
    2Moderate FAP/GLUT1 positivity
    3Strong FAP/GLUT1 positivity
  • TABLE 2.

    Patient Characteristics

    Patient no.Age (y)SexHistologyGradeUICC (initial)Date of initial diagnosisTumor sites on imaging (primary and metastatic)SUVmax
    68Ga-FAPI-4618F-FDG
    158MiCC3II01/2020Bone, lymph node14.36.3
    279FiCC3IIIA01/2021Liver17.55.1
    345MpCC2IIIC08/2020Liver14.58.0
    444MiCC3II07/2016Liver28.65.2
    557FdCC3IIIB03/2018Ductus hepaticus communis, peritoneal11.411.6
    670MpCC2II12/2019Liver, lymph node9.34.0
    740FiCC2IV04/2021Liver, peritoneal, lymph node25.4NA
    879FdCC2IIB03/2019NoneNANA
    954FiCC2IIIA03/2021Lymph node9.812.6
    1065FiCC2IIIB08/2020Lymph node7.79.2

    • UICC = Union for International Cancer Control; iCC = intrahepatic cholangiocarcinoma; pCC = perihilar cholangiocarcinoma; dCC = distal cholangiocarcinoma; NA = not available.

    • SUVmax was determined in hottest lesion for each tracer.

  • TABLE 3.

    Lesion-Based Detection Efficacy

    LocationOverallConventional CT18F-FDG PET/CT68Ga-FAPI-46 PET/CT
    Primary tumor5 (100)5 (100)5 (100)5 (100)
    Lymph nodes11 (100)3 (27.3)10 (90.9)11 (100)
    Distant metastases6 (100)2 (33.3)4 (66.7)6 (100)

    • Data are n followed by percentage in parentheses.

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