TY - JOUR
T1 - PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma
T2 - A Multicenter Inventory Study
AU - van Lith, Sanne A M
AU - Pruis, Ilanah J
AU - Tolboom, Nelleke
AU - Snijders, Tom J
AU - Henssen, Dylan
AU - Ter Laan, Mark
AU - Te Dorsthorst, Maarten
AU - Leenders, William P J
AU - Gotthardt, Martin
AU - Nagarajah, James
AU - Robe, Pierre A
AU - De Witt Hamer, Philip
AU - Hendrikse, Harry
AU - Oprea-Lager, Daniela E
AU - Yaqub, Maqsood
AU - Boellaard, Ronald
AU - Wesseling, Pieter
AU - Balvers, Rutger K
AU - Verburg, Frederik A
AU - Harteveld, Anita A
AU - Smits, Marion
AU - van den Bent, Martin
AU - van Zanten, Sophie E M Veldhuijzen
AU - van de Giessen, Elsmarieke
N1 - Publisher Copyright:
COPYRIGHT © 2023 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo (n 5 8) or recurrent (n 5 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [68Ga]Ga-PSMA-11 (n 5 7), 200 MBq of [18F]DCFpyl (n 5 3), or 200 MBq of [18F]PSMA-1007 (n 5 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples (n 5 40), determined using immunohistochemistry (n 5 35) or RNA sequencing (n 5 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUVmax, 1.3–20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1–359.0) calculated by dividing SUVmax of tumor by SUVmax of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r 5 20.173, P 5 0.320; for RNA, r 5 20.033, P 5 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodologic reasons, such as the inability to measure functionally active PSMA with immunohistochemistry, tracer pharmacokinetics, or the contribution of a disturbed blood–brain barrier to tracer retention, should still be investigated.
AB - Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo (n 5 8) or recurrent (n 5 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [68Ga]Ga-PSMA-11 (n 5 7), 200 MBq of [18F]DCFpyl (n 5 3), or 200 MBq of [18F]PSMA-1007 (n 5 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples (n 5 40), determined using immunohistochemistry (n 5 35) or RNA sequencing (n 5 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUVmax, 1.3–20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1–359.0) calculated by dividing SUVmax of tumor by SUVmax of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r 5 20.173, P 5 0.320; for RNA, r 5 20.033, P 5 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodologic reasons, such as the inability to measure functionally active PSMA with immunohistochemistry, tracer pharmacokinetics, or the contribution of a disturbed blood–brain barrier to tracer retention, should still be investigated.
KW - Endothelial Cells/metabolism
KW - Gallium Radioisotopes
KW - Glioblastoma/diagnostic imaging
KW - Humans
KW - Male
KW - Positron Emission Tomography Computed Tomography/methods
KW - Positron-Emission Tomography
KW - Prostate/pathology
KW - Prostatic Neoplasms/pathology
KW - RNA sequencing
KW - prostate-specific membrane antigen (PSMA)
KW - glioblastoma
KW - immunohistochemistry
KW - PET
UR - http://www.scopus.com/inward/record.url?scp=85173568326&partnerID=8YFLogxK
U2 - 10.2967/jnumed.123.265738
DO - 10.2967/jnumed.123.265738
M3 - Article
C2 - 37652540
SN - 0161-5505
VL - 64
SP - 1526
EP - 1531
JO - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
IS - 10
ER -