Review Article

Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors

Table 1

Summary of tissue expression of PSMA.

AuthorsYearTumor typeTissue stainMain results

Chang et al.19991GBM7E11 (Cytogen)
J591 (homemade)
J415 (homemade)
PEQ226.5 (Hybritech)
PM2J004.5 (Hybritech)
(i) All 5 anti-PSMA monoclonal antibodies react strongly with the neovasculature of GBM
(ii) No expression in tumor cells or normal brain tissue
Wernicke et al.201132GBMMouse Ab 3E6 (Dako)(i) 32/32 specimens stained for PSMA
(ii) 7/32 had 75-100% vascular staining, 15/32 had 51-75% staining, 2/32 had 26-50% staining, and 8/32 had 1-25% staining
(iii) 14/32 had 3+ staining intensity, 15/32 had 2+ intensity, and 3/32 had 1+ intensity
(iv) No expression in the vessels of normal brain
Wernicke et al.201414Breast cancer brain metastasesMouse Ab 3E6 (Dako)(i) 14/14 had PSMA-positive expression in metastasis vasculature
(ii) 14/14 had staining intensity of 2 (PSMA-positive in 50%+ tumor vessels)
Nomura et al.2014235 grade I gliomas
4 grade II gliomas
5 grade III gliomas
5 GBMs
4 breast cancer brain metastases
Mouse Ab 3E6 (Dako)(i) Grade I gliomas: moderate tumor vascular staining, some tumor cell staining
(ii) Grade II/III gliomas: light staining of some tumor cells (<2%), little/no vascular staining
(iii) GBMs: heavy tumor vascular staining
(iv) Breast cancer brain metastases: vascular staining, less than primary lesion, variable intensity within tumor
(v) No expression in normal brain vasculature
(vi) <5% expression in normal brain tissue
Schwenck et al.20151GBMUnknown(i) PSMA expression predominantly in tumor vascular endothelial cells
(ii) No PSMA expression in normal brain tissue or vasculature
Unterrainer et al.20171GliosarcomaUnknown(i) Strong PSMA expression in tumor vascular endothelial cells
(ii) No expression in tumor tissue
Salas Fragomeni et al.201731 anaplastic astrocytoma
2 GBMs
Unknown(i) Anaplastic astrocytoma: PSMA expression localized to tumor cells
(ii) GBMs: PSMA expression localized to tumor vasculature
(iii) No expression in normal brain tissue or vasculature
Saffar et al.20187210 grade I gliomas
26 grade II gliomas
9 grade III gliomas
27 GBMs
Mouse Ab 1D6 (Novocastra)(i) Grade I gliomas: 2/10 had PSMA expression, with staining intensity of 2; 8/10 had 0% extent of staining, 2 had 10-39% extent
(ii) Grade II gliomas: 1/26 had PSMA expression, with staining intensity of 25/26 had 0% extent of staining, 1 had >70% extent
(iii) Grade III gliomas: 1/9 had PSMA expression, with staining intensity of 1; 8/9 had 0% extent of staining, 1/9 had >70% extent
(iv) GBMs: 11/27 had PSMA expression; 9/27 had staining intensity of 1, 1/27 had intensity of 2, 1/27 had intensity of 3; 16/27 had 0% extent of staining, 4/27 had 1-9% extent, 5/27 had 10-39% extent, 1/27 had 40-69% extent, 1/27 had >70% extent
Matsuda et al.2018784 grade I gliomas
7 grade II gliomas
15 grade III gliomas
41 GBMs
4 brain metastases
7 PCNSLs
Rabbit mAb EPR6253 (Abcam)(i) Grade I gliomas: 3/4 had PSMA expression
(ii) Grade II gliomas: 1/7 had PSMA expression; 0/7 with high expression
(iii) Grade III gliomas: 10/15 had PSMA expression; 5/15 with high expression
(iv) GBMs: 40/41 had PSMA expression; 32/41 with high expression
(v) Brain metastases: 4/4 had PSMA expression; 3/4 with high expression
(vi) PCNSLs: 2/7 had PSMA expression
(vii) Radiation necrosis: 0/5 had PSMA expression
Mahzouni et al.201960GBMRabbit mAb SP29 (Biogenex)(i) 40/60 with PSMA expression in tumor vasculature
(ii) 3/60 with 76-100% extent of staining, 16/60 with 51-76% extent, 9/60 with 26-50% extent, 12/60 with 6-25% extent, 20/60 with <5% extent
(iii) 15/60 with severe intensity of staining, 23/60 with moderate intensity, 7/60 with mild intensity, 15 with zero intensity
(iv) No staining of normal brain vasculature
Oliveira et al.202038Rat glioma (with F98, 9L, or U87 cells)ab58779 (Abcam)
NBP1-89822 (Novus)
NBP1-45057 (Novus)
(i) Both 68Ga-PSMA and 18F-DCFPyL were expressed more in the peritumoral area than the tumor core, on ex vivo autoradiography
(ii) Higher TBR for 18F-DCFPyL (TBR 6.28-7.92) than 68Ga-PSMA (TBR 3.22-3.92) on PET
(iii) Heterogeneous tissue staining with 3 PSMA antibodies: ab58779 (Abcam) negative ×3, NBP1-45057 (Novus) positive ×3, and NBP1-89822 (Novus) split
(iv) Activated astrocyte expression (GFAP) was high peritumorally
Liu et al.20213014 grade II gliomas
4 grade III gliomas
12 GBMs
Unknown(i) PSMA-positive IHC staining in 0/14 grade II, 2/4 grade III, and 9/12 grade IV
Holzgreve et al.202116GBMMouse mAb 3E6 (Agilent)(i) PSMA expression in all GBMs at initial diagnosis and 15/16 at recurrence
(ii) Variable temporal evolution of PSMA expression from diagnosis to recurrence
(iii) High vascular PSMA expression at recurrence inversely associated with survival
(iv) Increasing PSMA expression over disease course inversely associated with survival
(v) No correlation between PSMA expression and MGMT or Ki-67