RT Journal Article
SR Electronic
T1 PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.123.265738
DO 10.2967/jnumed.123.265738
A1 van Lith, Sanne A.M.
A1 Pruis, Ilanah J.
A1 Tolboom, Nelleke
A1 Snijders, Tom J.
A1 Henssen, Dylan
A1 ter Laan, Mark
A1 te Dorsthorst, Maarten
A1 Leenders, William P.J.
A1 Gotthardt, Martin
A1 Nagarajah, James
A1 Robe, Pierre A.
A1 De Witt Hamer, Philip
A1 Hendrikse, Harry
A1 Oprea-Lager, Daniela E.
A1 Yaqub, Maqsood
A1 Boellaard, Ronald
A1 Wesseling, Pieter
A1 Balvers, Rutger K.
A1 Verburg, Frederik A.
A1 Harteveld, Anita A.
A1 Smits, Marion
A1 van den Bent, Martin
A1 van Zanten, Sophie E.M. Veldhuijzen
A1 van de Giessen, Elsmarieke
YR 2023
UL http://jnm.snmjournals.org/content/early/2023/08/31/jnumed.123.265738.abstract
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 = 8) or recurrent (n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [68Ga]Ga-PSMA-11 (n = 7), 200 MBq of [18F]DCFpyl (n = 3), or 200 MBq of [18F]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 (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 = −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.