PSMA Expression Assessed by PET Imaging Is a Required Biomarker for Selecting Patients for Any PSMA-Targeted Therapy

Abstract Introduction Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives. Methods Two independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET. Results Patients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET. Conclusions While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.

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Influence of androgen deprivation therapy on PSMA expression and PSMA-ligand PET imaging of prostate cancer patients

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-019-04529-8 ◽

2019 ◽

Vol 47 (1) ◽

pp. 9-15 ◽

Cited By ~ 4

Author(s):

Sofia Vaz ◽

Boris Hadaschik ◽

Michael Gabriel ◽

Ken Herrmann ◽

Matthias Eiber ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Androgen Deprivation Therapy ◽

Pet Imaging ◽

Androgen Deprivation ◽

Psma Ligand ◽

Psma Expression

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Value of Combined PET Imaging with [18F]FDG and [68Ga]Ga-PSMA-11 in mCRPC Patients with Worsening Disease during [177Lu]Lu-PSMA-617 RLT

Cancers ◽

10.3390/cancers13164134 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4134

Author(s):

Fadi Khreish ◽

Kalle Ribbat ◽

Mark Bartholomä ◽

Stephan Maus ◽

Tobias Stemler ◽

...

Keyword(s):

Pet Imaging ◽

Median Overall Survival ◽

Metabolic Tumor Volume ◽

Total Lesion Glycolysis ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

18F Fdg ◽

Poor Outcomes ◽

Specific Membrane ◽

Psma Expression

Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC), some patients show worsening disease during PSMA-RLT. We investigated the value of combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging in this setting. In n = 29 mCRPC patients with worsening disease after a median of four cycles of [177Lu]Lu-PSMA-617 RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging was performed to detect [18F]FDG-avid lesions with low or no PSMA expression (mismatch lesions). To evaluate prognostic implication of mismatch, survival analyses regarding presence, location, and [18F]FDG PET-derived parameters such as SUVmax, metabolic tumor volume (MTVm), and total lesion glycolysis (TLGm) of mismatch findings were performed. Seventeen patients (59%) showed at least one mismatch metastasis. From the time point of combined PET imaging, the median overall survival (OS) of patients with mismatch findings was significantly (p = 0.008) shorter than those without (3.3 vs. 6.1 mo). Patients with a high MTVm revealed a significantly (p = 0.034) shorter OS of 2.6 mo than patients with low MTVm (5.3 mo). Furthermore, patients with hepatic mismatch showed a significantly (p = 0.049) shorter OS than those without (2.9 vs. 5.3 mo). Difference in OS regarding SUVmax and TLGm was not significant. In mCRPC patients with worsening disease during PSMA-RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging is essential to identify mismatch findings, as these are associated with poor outcomes requiring a change in therapy management.

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Single-lesion PSMA protein expression and response to Lu-177 PSMA therapy in patients with castration-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5065 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5065-5065

Author(s):

Judith Stangl-Kremser ◽

Sazan Rasul ◽

Jeffrey J. Tosoian ◽

Simpa Salami ◽

Alexander Zaslavsky ◽

...

Keyword(s):

Prostate Cancer ◽

Protein Expression ◽

Pet Imaging ◽

Metastatic Tumor ◽

Specific Response ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Tumor Tissues ◽

Psma Pet ◽

Psma Expression

5065 Background: The recent introduction of Lu-177 PSMA for the treatment of castration-resistant prostate cancer (CRPC) has been met with much excitement. Initial reports of clinical response are promising, despite known inter- and intra-patient molecular heterogeneity. In this study, we examined the utility of PSMA protein expression in metastatic tumor tissues as a predictor of lesion-specific response to Lu-177 PSMA therapy in men with CRPC. Methods: Between 2015-2020, 19 patients with metastases at multiple sites underwent metastatic lesion biopsy, Ga-68 PSMA PET imaging, and subsequent treatment with three cycles of Lu-177 PSMA. A monoclonal anti-PSMA antibody (EPITOMICS (USA), 1:50) was used to semi-quantitatively assess PSMA protein expression in the biopsy specimen. The histoscore (range 0-300) was derived from intensity and extent of the immunohistochemistry staining and was determined by experienced genitourinary pathologists. Imaging evaluation was performed according to the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria. We assessed the association of the PSMA protein expression in metastatic tumor tissues and the lesion-specific response to Lu-177 PSMA therapy. Results: In 12 patients with biopsy specimens available for staining, PSMA expression correlated with enhancement (SUVmax) of the biopsy site on Ga-68 PSMA PET imaging (rs = 0.63). Of the nine patients with repeat imaging after Lu-177 PSMA therapy, five (55.6%) had a lesion-specific response at the site of biopsy. PSMA expression on immunohistochemistry was unable to accurately predict lesion-specific response in univariable analysis (p = 0.81, 95% CI 94.6-76.6). Among the five men with a lesion-specific response, three (60%) experienced overall progression based on PERCIST. There was no association between lesion-specific response and overall progression (p = 0.64). Conclusions: In patients with multiple metastases, PSMA protein expression from a single site biopsy was not predictive of site-specific Lu-177 PSMA response based on PERCIST. Additional studies are necessary to further interrogate the clinical consequence of PSMA expression heterogeneity in metastatic sites as well as the mechanisms underpinning resistance to Lu-177 PSMA in patients with CRPC.

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PET Imaging of β-Glucuronidase Activity by an Activity-Based 124I-Trapping Probe for the Personalized Glucuronide Prodrug Targeted Therapy

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-14-0212 ◽

2014 ◽

Vol 13 (12) ◽

pp. 2852-2863 ◽

Cited By ~ 9

Author(s):

Yu-Cheng Su ◽

Ta-Chun Cheng ◽

Yu-Ling Leu ◽

Steve R. Roffler ◽

Jaw-Yuan Wang ◽

...

Keyword(s):

Targeted Therapy ◽

Pet Imaging ◽

Glucuronidase Activity

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PSMA Expression in Glioblastoma as a Basis for Theranostic Approaches: A Retrospective, Correlational Panel Study Including Immunohistochemistry, Clinical Parameters and PET Imaging

Frontiers in Oncology ◽

10.3389/fonc.2021.646387 ◽

2021 ◽

Vol 11 ◽

Author(s):

Adrien Holzgreve ◽

Annamaria Biczok ◽

Viktoria C. Ruf ◽

Friederike Liesche-Starnecker ◽

Katja Steiger ◽

...

Keyword(s):

Endothelial Cells ◽

Pet Imaging ◽

Methylation Status ◽

Panel Study ◽

Initial Diagnosis ◽

Vascular Density ◽

Clinical Parameters ◽

Recurrent Tumor ◽

Psma Pet ◽

Psma Expression

AimThe aim of the current study was to enlighten the evolution of prostate-specific membrane antigen (PSMA) expression in glioblastoma between initial diagnosis and recurrence in order to provide preliminary insight for further clinical investigations into innovative PSMA-directed treatment concepts in neuro-oncology.MethodsPatients who underwent resection for de-novo glioblastoma (GBM) and had a re-resection in case of a recurrent tumor following radiochemotherapy and subsequent chemotherapy were included (n = 16). Histological and immunohistochemical stainings were performed at initial diagnosis and at recurrence (n = 96 tissue specimens). Levels of PSMA expression both in endothelial and non-endothelial cells as well as vascular density (CD34) were quantified via immunohistochemistry and changes between initial diagnosis and recurrence were determined. Immunohistochemical findings were correlated with survival and established clinical parameters.ResultsPSMA expression was found to be present in all GBM tissue samples at initial diagnosis as well as in all but one case of recurrent tumor samples. The level of PSMA expression in glioblastoma varied inter-individually both in endothelial and non-endothelial cells. Likewise, the temporal evolution of PSMA expression highly varied in between patients. The level of vascular PSMA expression at recurrence and its change between initial diagnosis and recurrence was associated with post recurrence survival time: Patients with high vascular PSMA expression at recurrence as well as patients with increasing PSMA expression throughout the disease course survived shorter than patients with low vascular PSMA expression or decreasing vascular PSMA expression. There was no significant correlation of PSMA expression with MGMT promoter methylation status or Ki-67 labelling index.ConclusionPSMA is expressed in glioblastoma both at initial diagnosis and at recurrence. High vascular PSMA expression at recurrence seems to be a negative prognostic marker. Thus, PSMA expression in GBM might present a promising target for theranostic approaches in recurrent glioblastoma. Especially PSMA PET imaging and PSMA-directed radioligand therapy warrant further studies in brain tumor patients.

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PET Imaging Biomarkers of Anti-EGFR Immunotherapy in Esophageal Squamous Cell Carcinoma Models

Cells ◽

10.3390/cells7110187 ◽

2018 ◽

Vol 7 (11) ◽

pp. 187

Author(s):

Tae Lee ◽

In Song ◽

Jong Shin ◽

Yong Park ◽

Jung Kim ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Targeted Therapy ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Pet Imaging ◽

Fdg Pet ◽

Imaging Biomarkers ◽

Egfr Expression ◽

18F Fdg

Epidermal growth factor receptor (EGFR) is overexpressed and considered as a proper molecular target for diagnosis and targeted therapy of esophageal squamous cell carcinoma (ESCC). This study evaluated the usefulness of PET imaging biomarkers with 64Cu-PCTA-cetuximab and 18F-FDG-PET for anti-EGFR immunotherapy in ESCC models. In vivo EGFR status and glucose metabolism by cetuximab treatment were evaluated using 64Cu-PCTA-cetuximab and 18F-FDG-PET, respectively. Therapeutic responses with imaging biomarkers were confirmed by western blot and immunohistochemistry. TE-4 and TE-8 tumors were clearly visualized by 64Cu-PCTA-cetuximab, and EGFR expression on TE-8 tumors showed 2.6-fold higher uptake than TE-4. Tumor volumes were markedly reduced by cetuximab in TE-8 tumor (92.5 ± 5.9%), but TE-4 tumors were refractory to cetuximab treatment. The SUVs in 64Cu-PCTA-cetuximab and 18F-FDG-PET images were statistically significantly reduced by cetuximab treatment in TE-8 but not in TE-4. 64Cu-PCTA-cetuximab and 18F-FDG-PET images were well correlated with EGFR and pAkt levels. 64Cu-PCTA-cetuximab immuno-PET had a potential for determining EGFR level and monitoring therapeutic response by anti-EGFR therapy. 18F-FDG-PET was also attractive for monitoring efficacy of anti-EGFR therapy. In conclusion, PET imaging biomarkers may be useful for selecting patients that express target molecules and for monitoring therapeutic efficacy of EGFR-targeted therapy in ESCC patients.

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