학술논문
PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study.
Document Type
Academic Journal
Author
van Lith SAM; Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands.; Pruis IJ; Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.; Tolboom N; Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.; Snijders TJ; Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Henssen D; Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands.; Ter Laan M; Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands.; Te Dorsthorst M; Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands.; Leenders WPJ; Biochemistry, Radboud University Medical Center, Nijmegen, The Netherlands.; Predica Diagnostics, Nijmegen, The Netherlands.; Gotthardt M; Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands.; Nagarajah J; Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands.; Robe PA; Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands.; De Witt Hamer P; Neurosurgery, Amsterdam UMC, VUmc, Amsterdam, The Netherlands.; Hendrikse H; Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands.; Oprea-Lager DE; Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands.; Yaqub M; Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands.; Boellaard R; Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands.; Wesseling P; Pathology, Amsterdam UMC, VUmc, Amsterdam, The Netherlands.; Pathology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Balvers RK; Neurosurgery, Erasmus MC, Rotterdam, The Netherlands.; Verburg FA; Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.; Harteveld AA; Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.; Smits M; Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.; Medical Delta, Delft, The Netherlands; and.; van den Bent M; Brain Tumor Center at Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.; van Zanten SEMV; Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; s.veldhuijzenvanzanten@erasmusmc.nl.; van de Giessen E; Radiology and Nuclear Medicine, Amsterdam UMC, VUmc, Amsterdam, The Netherlands.
Source
Publisher: Society of Nuclear Medicine Country of Publication: United States NLM ID: 0217410 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-5667 (Electronic) Linking ISSN: 01615505 NLM ISO Abbreviation: J Nucl Med Subsets: MEDLINE
Subject
Language
English
Abstract
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 = 8) or recurrent ( n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [ 68 Ga]Ga-PSMA-11 ( n = 7), 200 MBq of [ 18 F]DCFpyl ( n = 3), or 200 MBq of [ 18 F]PSMA-1007 ( n = 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 = 40), determined using immunohistochemistry ( n = 35) or RNA sequencing ( n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUV max , 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 SUV max of tumor by SUV max 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 = -0.173, P = 0.320; for RNA, r = -0.033, P = 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.
(© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
(© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)