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Research ArticleClinical Investigation

PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study

Sanne A.M. van Lith, Ilanah J. Pruis, Nelleke Tolboom, Tom J. Snijders, Dylan Henssen, Mark ter Laan, Maarten te Dorsthorst, William P.J. Leenders, Martin Gotthardt, James Nagarajah, Pierre A. Robe, Philip De Witt Hamer, Harry Hendrikse, Daniela E. Oprea-Lager, Maqsood Yaqub, Ronald Boellaard, Pieter Wesseling, Rutger K. Balvers, Frederik A. Verburg, Anita A. Harteveld, Marion Smits, Martin van den Bent, Sophie E.M. Veldhuijzen van Zanten and Elsmarieke van de Giessen
Journal of Nuclear Medicine August 2023, jnumed.123.265738; DOI: https://doi.org/10.2967/jnumed.123.265738
Sanne A.M. van Lith
1Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands;
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Ilanah J. Pruis
2Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands;
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Nelleke Tolboom
3Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands;
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Tom J. Snijders
4Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands;
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Dylan Henssen
1Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands;
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Mark ter Laan
5Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands;
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Maarten te Dorsthorst
5Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands;
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William P.J. Leenders
6Biochemistry, Radboud University Medical Center, Nijmegen, The Netherlands;
7Predica Diagnostics, Nijmegen, The Netherlands;
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Martin Gotthardt
1Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands;
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James Nagarajah
1Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands;
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Pierre A. Robe
4Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands;
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Philip De Witt Hamer
8Neurosurgery, Amsterdam UMC, VUmc, Amsterdam, The Netherlands;
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Harry Hendrikse
9Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands;
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Daniela E. Oprea-Lager
9Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands;
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Maqsood Yaqub
9Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands;
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Ronald Boellaard
9Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands;
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Pieter Wesseling
10Pathology, Amsterdam UMC, VUmc, Amsterdam, The Netherlands;
11Pathology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands;
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Rutger K. Balvers
12Neurosurgery, Erasmus MC, Rotterdam, The Netherlands;
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Frederik A. Verburg
2Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands;
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Anita A. Harteveld
2Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands;
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Marion Smits
2Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands;
13Medical Delta, Delft, The Netherlands; and
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Martin van den Bent
14Brain Tumor Center at Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands
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Sophie E.M. Veldhuijzen van Zanten
2Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands;
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Elsmarieke van de Giessen
9Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands;
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  • FIGURE 1.
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    FIGURE 1.

    Selected examples of PET (A, D, G, and J), MRI (B, E, H, and K), hybrid PET/MRI (C), and fused PET/MRI (F, I, and L) of patients injected with [68Ga]Ga-PSMA-11 (patient 1 from Erasmus MC [A–C], SUVmax, 20.0, and patient 10 from UMCU [G–I], SUVmax, 1.3), [18F]DCFpyl (patient 8 from Amsterdam UMC [D–F], SUVmax, 13.1), and [18F]PSMA-1007 (patient 14 from Radboudumc [J–L], SUVmax, 12.4). Note heterogeneity of tracer uptake within tumors.

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    FIGURE 2.

    (A) Time–activity curves showing tumor uptake of [18F]DCFpyl (orange) and [68Ga]Ga-PSMA (blue) in MBq/mL from 0 to 240 min after injection for patients 1–8 (each marker icon represents one patient). Representative images of early (B, blue contour) and late (C, red contour) perfusion in first 2 min after injection of [18F]DCFpyl in patient 6.

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    FIGURE 3.

    Representative images of PSMA immunohistochemistry in formalin-fixed and paraffin-embedded biopsy samples. (A) Positive, dispersed individual cells of unknown origin in periphery of tumor and positive vasculature in tumor cell–dense region. (B) Positive vasculature in tumor cell–dense region. (C) Positive, dispersed individual cells and granular staining in neuropil. (D) Positive individual cells and strong granular staining in neuropil. To exemplify method used for scoring IHC findings, following scores would have been given for these snapshot figures for microvasculature, individual cells, and granular staining in neuropil (sum score), respectively: 2, 3, and 1 (sum, 6) (A); 4, 0, and 0 (sum, 4) (B); 0, 3, and 3 (sum, 6) (C); and 0, 4, and 4 (sum, 8) (D). (E) Correlation between total IHC score and tracer uptake. (F) Correlation between normalized RNA expression of FOLH1 (PSMA-encoding gene) and tracer uptake. Tracer uptake is expressed in SUVmax and measured on PET in 1-cm spheric volumes of interest in region on scan where biopsies were performed. IHC = immunohistochemistry; FOLH1 = folate hydrolase 1; FPM = fragments per million.

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    TABLE 1.

    Tumor Uptake of Various PSMA-Targeting Tracers

    No.RadioligandTime after injection (min)SUVmaxSUVmeanTBRmax/max
    1[68Ga]Ga-PSMA-1190 (WB)15.34.432.6
    16520.04.566.7
    24017.04.038.6
    2[68Ga]Ga-PSMA-1190 (WB)3.61.7359.0
    1655.92.9295.0
    2405.82.835.9
    3[68Ga]Ga-PSMA-1190 (WB)7.42.5185.3
    1659.82.698.4
    24010.02.826.3
    4[68Ga]Ga-PSMA-1190 (WB)6.53.110.3
    1659.03.517.3
    2409.03.67.5
    5[68Ga]Ga-PSMA-1190 (WB)7.31.966.6
    1657.72.329.5
    2409.02.664.6
    6[18F]DCFPyl804.52.121.9
    NA (WB)NANANA
    1406.82.925.7
    7[18F]DCFPyl805.32.123.5
    95 (WB)4.52.313.6
    1407.42.724.4
    8[18F]DCFPyl8010.34.634.8
    95 (WB)12.65.329.9
    14013.16.036.5
    9[68Ga]Ga-PSMA-11602.21.072.3
    10[68Ga]Ga-PSMA-11601.30.610.3
    11[18F]PSMA-10071203.41.66.1
    12[18F]PSMA-10071208.13.410.1
    13[18F]PSMA-100712014.66.839.6
    14[18F]PSMA-100712012.44.77.8
    • TBRmax/max = SUVmax tumor divided by SUVmax background; WB = whole body; NA = not available.

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Journal of Nuclear Medicine: 66 (5)
Journal of Nuclear Medicine
Vol. 66, Issue 5
May 1, 2025
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PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study
Sanne A.M. van Lith, Ilanah J. Pruis, Nelleke Tolboom, Tom J. Snijders, Dylan Henssen, Mark ter Laan, Maarten te Dorsthorst, William P.J. Leenders, Martin Gotthardt, James Nagarajah, Pierre A. Robe, Philip De Witt Hamer, Harry Hendrikse, Daniela E. Oprea-Lager, Maqsood Yaqub, Ronald Boellaard, Pieter Wesseling, Rutger K. Balvers, Frederik A. Verburg, Anita A. Harteveld, Marion Smits, Martin van den Bent, Sophie E.M. Veldhuijzen van Zanten, Elsmarieke van de Giessen
Journal of Nuclear Medicine Aug 2023, jnumed.123.265738; DOI: 10.2967/jnumed.123.265738

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PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study
Sanne A.M. van Lith, Ilanah J. Pruis, Nelleke Tolboom, Tom J. Snijders, Dylan Henssen, Mark ter Laan, Maarten te Dorsthorst, William P.J. Leenders, Martin Gotthardt, James Nagarajah, Pierre A. Robe, Philip De Witt Hamer, Harry Hendrikse, Daniela E. Oprea-Lager, Maqsood Yaqub, Ronald Boellaard, Pieter Wesseling, Rutger K. Balvers, Frederik A. Verburg, Anita A. Harteveld, Marion Smits, Martin van den Bent, Sophie E.M. Veldhuijzen van Zanten, Elsmarieke van de Giessen
Journal of Nuclear Medicine Aug 2023, jnumed.123.265738; DOI: 10.2967/jnumed.123.265738
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Keywords

  • Glioblastoma
  • prostate-specific membrane antigen (PSMA)
  • PET
  • immunohistochemistry
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