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Research ArticleTheranostics

Radiation Dosimetry and Biodistribution of 68Ga-FAPI-46 PET Imaging in Cancer Patients

Catherine Meyer, Magnus Dahlbom, Thomas Lindner, Sebastien Vauclin, Christine Mona, Roger Slavik, Johannes Czernin, Uwe Haberkorn and Jeremie Calais
Journal of Nuclear Medicine August 2020, 61 (8) 1171-1177; DOI: https://doi.org/10.2967/jnumed.119.236786
Catherine Meyer
1Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, UCLA, Los Angeles, California
2Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California
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Magnus Dahlbom
1Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, UCLA, Los Angeles, California
2Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California
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Thomas Lindner
3Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
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Sebastien Vauclin
4DOSIsoft SA, Cachan, France
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Christine Mona
2Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California
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Roger Slavik
1Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, UCLA, Los Angeles, California
2Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California
5Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
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Johannes Czernin
2Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California
6Institute of Urologic Oncology, UCLA, Los Angeles, California
7Clinical Cooperation Unit Nuclear Medicine, DKFZ Heidelberg, Heidelberg, Germany; and
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Uwe Haberkorn
3Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany
7Clinical Cooperation Unit Nuclear Medicine, DKFZ Heidelberg, Heidelberg, Germany; and
8Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany
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Jeremie Calais
1Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, UCLA, Los Angeles, California
2Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California
5Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
6Institute of Urologic Oncology, UCLA, Los Angeles, California
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  • FIGURE 1.
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    FIGURE 1.

    Delineated volumes used for determination of renal cortex volume: entire kidney volume (A) from which urine, including in renal calyces, is subtracted (B) to yield renal cortex volume (C). Images are shown for patient 6 and are representative of method applied for all patients. All volumes are shown in axial (top), coronal (middle), and maximum-intensity-projection views (bottom).

  • FIGURE 2.
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    FIGURE 2.

    Percentage injected activity curves for patient 3 are shown for various source organs. Solid circles are measured values, and dotted lines are monoexponential functions fit to data.

  • FIGURE 3.
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    FIGURE 3.

    Patient 3 (female). (A) 68Ga-FAPI-46 maximum-intensity projections and delineated organs for dose calculations. (B) SUVmax at 3 time points after tracer injection. (C) TBR at 3 time points after tracer injection. SUVmax and TBR for bladder are excluded from plot. Data values are available in Supplemental Table 1.

  • FIGURE 4.
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    FIGURE 4.

    Patient 5 (male). (A) 68Ga-FAPI-46 maximum-intensity projection and delineated organs for dose calculations. (B) SUVmax at 3 time points after tracer injection. (C) TBR at 3 time points after tracer injection. SUVmax and TBR for bladder are excluded from plot. Data values are available in Supplemental Table 1.

  • FIGURE 5.
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    FIGURE 5.

    Pooled tumor and organ SUVmax (A) and TBR (B) at 3 time points after tracer injection (excluding bladder). Results are shown as mean and SD for 6 patients. Data values are available in Table 4.

Tables

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    TABLE 1

    Patient Characteristics

    Patient no.SexAge (y)DiagnosisInjected activity (MBq)
    1F63Cholangiocellular carcinoma246
    2M81Pancreatic cancer with peritonitis carcinomatosa240
    3F78Breast cancer234
    4M56Oropharynx carcinoma239
    5M78Head and neck cancer214
    6M62Gastric cancer243
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    TABLE 2

    Monoexponential Function Fitting Parameters and Time-Integrated Activity Coefficients (Residence Times) for 68Ga-FAPI-46 in Various Organs

    OrganA (%IA)λ (h−1)TIAC (h)
    Liver3.49 (2.26)0.88 (0.12)0.0378 (0.0198)
    Kidney2.07 (0.65)1.08 (0.26)0.0195 (0.0062)
    Bladder6.82 (2.32)1.47 (0.91)0.0595 (0.0319)
    Heart1.69 (0.30)0.94 (0.06)0.0182 (0.0035)
    Spleen0.71 (0.62)0.96 (0.12)0.0074 (0.0066)
    Marrow2.61 (0.63)2.05 (2.97)0.0250 (0.0114)
    Uterus (n = 2)0.13 (0.004)0.50 (0.07)0.0027 (0.0005)
    • A = activity, expressed as %IA = percentage injected activity; Embedded Image; λ = rate constant; TIAC = time-integrated activity coefficient.

    • Data are mean followed by SD in parentheses for 6 patients. Representative percentage injected activity curves with monoexponential curve fits overlaid are available in Supplemental Figure 1. Per-patient coefficients and TIACs are available in Supplemental Table 2.

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    TABLE 3

    68Ga-FAPI-46 Dosimetry Summary of Mean Absorbed and Effective Doses Using OLINDA/EXM

    OrganDose per injected activity (mGy/MBq)Effective dose per injected activity (mSv/MBq)
    Adrenals5.60E−03 (8.12E−04)2.80E−05 (4.04E−06)
    Brain4.59E−03 (6.12E−04)2.29E−05 (3.06E−06)
    Breasts4.55E−03 (6.47E−04)2.28E−04 (3.23E−05)
    Gallbladder wall5.62E−03 (8.53E−04)—
    Lower large intestine wall5.72E−03 (6.96E−04)6.86E−04 (8.33E−05)
    Small intestine5.48E−03 (6.37E−04)2.74E−05 (3.20E−06)
    Stomach wall5.32E−03 (7.25E−04)6.38E−04 (8.69E−05)
    Upper large intestine wall5.47E−03 (6.97E−04)2.74E−05 (3.50E−06)
    Heart wall1.11E−02 (1.26E−03)—
    Kidneys1.60E−02 (4.60E−03)7.98E−05 (2.29E−05)
    Liver1.01E−02 (7.96E−03)5.05E−04 (4.00E−04)
    Lungs5.02E−03 (7.09E−04)6.02E−04 (8.48E−05)
    Muscle4.96E−03 (6.54E−04)2.48E−05 (3.27E−06)
    Ovaries5.76E−03 (6.91E−04)1.15E−03 (1.38E−04)
    Pancreas5.69E−03 (8.49E−04)2.84E−05 (4.24E−06)
    Red marrow7.08E−03 (1.00E−03)8.49E−04 (1.20E−04)
    Osteogenic cells9.38E−03 (1.30E−03)9.38E−05 (1.30E−05)
    Skin4.41E−03 (6.33E−04)4.41E−05 (6.33E−06)
    Spleen6.96E−03 (2.76E−03)3.48E−05 (1.39E−05)
    Testes4.88E−03 (6.69E−04)1.15E−03 (1.38E−04)
    Thymus5.10E−03 (6.40E−04)2.55E−05 (3.21E−06)
    Thyroid4.84E−03 (5.72E−04)2.42E−04 (2.85E−05)
    Urinary bladder wall4.83E−02 (8.55E−03)2.41E−03 (4.27E−04)
    Uterus9.54E−03 (5.36E−03)4.76E−05 (2.67E−05)
    Total body5.82E−03 (1.18E−03)7.80E−03 (1.31E−03)
    Total body dose for 200 MBq1.16 mGy (0.24 mGy)1.56 mSv (0.26 mSv)
    • Data are mean followed by SD in parentheses for 6 patients. Effective doses in ovaries and testes are equivalent because of use of hermaphroditic adult phantom weighting. Gallbladder wall and heart wall effective doses are not available based on ICRP radiation weighting factors. Nonpooled OLINDA/EXM reports, including β and photon contribution to total dose, are available in Supplemental Table 3.

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    TABLE 4

    Pooled Tumor-to-Organ SUV Ratio, SUVmax, and SUVmean at 3 Time Points After 68Ga-FAPI-46 Administration

    Parameter10 min1.2 h3.3 h
    SUVmax-to-SUVmean ratio
     Tumor-to-liver12.28 (5.75)14.79 (6.22)16.80 (6.90)
     Tumor-to-kidney8.17 (2.76)9.96 (3.64)10.68 (5.34)
     Tumor-to-blood10.89 (3.61)14.15 (5.02)15.87 (7.30)
     Tumor-to-muscle10.71 (3.56)15.91 (6.33)22.77 (9.15)
     Tumor-to-heart11.78 (3.76)15.48 (5.49)19.11 (7.44)
     Tumor-to-spleen13.27 (4.31)17.44 (6.36)18.99 (7.27)
     Tumor-to-marrow21.46 (7.56)25.96 (8.09)31.13 (9.52)
     Tumor-to-uterus (n = 2)9.60 (0.46)6.19 (2.12)6.20 (2.70)
    SUVmax
     Tumor15.54 (5.13)14.89 (5.77)13.39 (6.44)
     Liver7.42 (6.84)5.15 (3.56)5.04 (2.07)
     Kidney3.00 (0.89)2.33 (0.26)2.08 (0.49)
     Blood1.77 (0.35)1.38 (0.26)1.37 (0.31)
     Muscle1.87 (0.49)1.37 (0.45)1.24 (0.56)
     Heart3.28 (1.00)2.48 (1.17)3.02 (1.31)
     Spleen2.30 (0.23)1.94 (0.42)2.88 (1.38)
     Marrow1.77 (0.34)1.85 (1.05)2.00 (0.59)
     Uterus (n = 2)3.37 (0.23)4.61 (0.32)4.42 (0.58)
    SUVmean
     Tumor3.87 (1.30)3.37 (1.11)2.81 (1.44)
     Liver1.51 (0.96)1.10 (0.58)0.81 (0.34)
     Kidney1.92 (0.34)1.47 (0.17)1.25 (0.22)
     Blood1.43 (0.25)1.03 (0.15)0.83 (0.15)
     Muscle1.48 (0.41)0.96 (0.32)0.61 (0.24)
     Heart1.32 (0.21)0.95 (0.15)0.68 (0.15)
     Spleen1.17 (0.20)0.85 (0.17)0.69 (0.16)
     Marrow0.73 (0.12)0.56 (0.11)0.41 (0.10)
     Uterus (n = 2)2.08 (0.27)2.53 (0.24)1.97 (0.42)
    • Data are mean followed by SD in parentheses for 6 patients.

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Journal of Nuclear Medicine: 61 (8)
Journal of Nuclear Medicine
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August 1, 2020
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Radiation Dosimetry and Biodistribution of 68Ga-FAPI-46 PET Imaging in Cancer Patients
Catherine Meyer, Magnus Dahlbom, Thomas Lindner, Sebastien Vauclin, Christine Mona, Roger Slavik, Johannes Czernin, Uwe Haberkorn, Jeremie Calais
Journal of Nuclear Medicine Aug 2020, 61 (8) 1171-1177; DOI: 10.2967/jnumed.119.236786

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Radiation Dosimetry and Biodistribution of 68Ga-FAPI-46 PET Imaging in Cancer Patients
Catherine Meyer, Magnus Dahlbom, Thomas Lindner, Sebastien Vauclin, Christine Mona, Roger Slavik, Johannes Czernin, Uwe Haberkorn, Jeremie Calais
Journal of Nuclear Medicine Aug 2020, 61 (8) 1171-1177; DOI: 10.2967/jnumed.119.236786
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