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

Holzgreve, Adrien; Biczok, Annamaria; Ruf, Viktoria; Liesche‐Starnecker, Friederike; Steiger, Katja; Kirchner, Maximilian A.; Mittlmeier, Lena M.; Herms, Jochen; Schlegel, Jürgen; Bartenstein, Peter; Tonn, Jörg‐Christian; Albert, Nathalie L.; Suchorska, Bogdana

doi:10.3389/fonc.2021.646387

Cited by 47 publications

(52 citation statements)

References 51 publications

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“…It has to be noted, that only an 18 F-labeled tracer has been used and no full dosimetry with a therapeutic tracer has been performed. Nevertheless, the current findings point to the inherent importance of a strictly theranostic approach for the investigation of PSMA radioligand therapy, since PSMA uptake does not appear to be present in all murine GBM, consistent with a highly heterogeneous PSMA expression in human GBM ( 38 ). While tumor-to-background contrast has been reported to be high in multiple studies ( 17 – 21 ) the absolute uptake values between patients vary considerably [e.g.…”

Section: Discussionmentioning

confidence: 57%

PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook

et al. 2021

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BackgroundProstate specific membrane antigen (PSMA) PET imaging has recently gained attention in glioblastoma (GBM) patients as a potential theranostic target for PSMA radioligand therapy. However, PSMA PET has not yet been established in a murine GBM model. Our goal was to investigate the potential of PSMA PET imaging in the syngeneic GL261 GBM model and to give an outlook regarding the potential of PMSA radioligand therapy in this model.MethodsWe performed an 18F-PSMA-1007 PET study in the orthotopic GL261 model (n=14 GBM, n=7 sham-operated mice) with imaging at day 4, 8, 11, 15, 18 and 22 post implantation. Time-activity-curves (TAC) were extracted from dynamic PET scans (0-120 min p. i.) in a subset of mice (n=4 GBM, n=3 sham-operated mice) to identify the optimal time frame for image analysis, and standardized-uptake-values (SUV) as well as tumor-to-background ratios (TBR) using contralateral normal brain as background were calculated in all mice. Additionally, computed tomography (CT), ex vivo and in vitro18F-PSMA-1007 autoradiographies (ARG) were performed.ResultsTAC analysis of GBM mice revealed a plateau of TBR values after 40 min p. i. Therefore, a 30 min time frame between 40-70 min p. i. was chosen for PET quantification. At day 15 and later, GBM mice showed a discernible PSMA PET signal on the inoculation site, with highest TBRmean in GBM mice at day 18 (7.3 ± 1.3 vs. 1.6 ± 0.3 in shams; p=0.024). Ex vivo ARG confirmed high tracer signal in GBM compared to healthy background (TBRmean 26.9 ± 10.5 vs. 1.6 ± 0.7 in shams at day 18/22 post implantation; p=0.002). However, absolute uptake values in the GL261 tumor remained low (e.g., SUVmean 0.21 ± 0.04 g/ml at day 18) resulting in low ratios compared to dose-relevant organs (e.g., mean tumor-to-kidney ratio 1.5E-2 ± 0.5E-2).ConclusionsAlthough 18F-PSMA-1007 PET imaging of GL261 tumor-bearing mice is feasible and resulted in high TBRs, absolute tumoral uptake values remained low and hint to limited applicability of the GL261 model for PSMA-directed therapy studies. Further investigations are warranted to identify suitable models for preclinical evaluation of PSMA-targeted theranostic approaches in GBM.

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Section: Discussionmentioning

confidence: 57%

PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook

et al. 2021

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“…With regard to prostate carcinoma, it is well known that there is a close correlation between tracer uptake on 68 Ga-PSMA-PET/CT and PSMA expression in IHC [42]. In contrast, a case study of a glioblastoma was recently published in which a low tracer accumulation was seen in 68 Ga-PSMA-PET/CT despite an intermediate PSMA expression in IHC [43]. One possible reason for this discrepancy could be that PSMA expression in apical membranes-typical for prostate carcinoma cells-is connected with a higher tracer uptake on PET imaging than the level of PSMA expression in cytoplasm, which is often observed in nonprostatic disease [44].…”

Section: Discussionmentioning

confidence: 99%

Prostate-Specific Membrane Antigen in Anaplastic and Poorly Differentiated Thyroid Cancer—A New Diagnostic and Therapeutic Target?

Wächter

Fazio

Maurer

et al. 2021

Cancers

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Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (68Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (18F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients’ tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. 68Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), 18F-FDG-PET/CT tracer uptake was positive and 68Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (177Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on 68Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of 18F-FDG-PET/CT in comparison to 68Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that 68Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established 18F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by 18F-FDG-PET/CT and to determine patients’ eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.

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“…Nevertheless, several PET and SPECT studies with radiolabeled PSMAPET radiotracers were also performed in patients with thyroid cancer [83], hepatocellular carcinoma [84], prostate adenocarcinoma [85], glioblastoma [86], myeloma [87], sinonasal glomangioperi-cytoma [88], Sjögren syndrome [89], and bladder cancer [90], which shows PSMA-targeted radiotracers are now playing an increasing role in the diagnostic imaging of patients.…”

Section: Prostate-specific Membrane Antigen (Psma)mentioning

confidence: 99%

Role of Peptides in Diagnostics

Pandey

Malviya

Dvoráková

2021

IJMS

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The specificity of a diagnostic assay depends upon the purity of the biomolecules used as a probe. To get specific and accurate information of a disease, the use of synthetic peptides in diagnostics have increased in the last few decades, because of their high purity profile and ability to get modified chemically. The discovered peptide probes are used either in imaging diagnostics or in non-imaging diagnostics. In non-imaging diagnostics, techniques such as Enzyme-Linked Immunosorbent Assay (ELISA), lateral flow devices (i.e., point-of-care testing), or microarray or LC-MS/MS are used for direct analysis of biofluids. Among all, peptide-based ELISA is considered to be the most preferred technology platform. Similarly, peptides can also be used as probes for imaging techniques, such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET). The role of radiolabeled peptides, such as somatostatin receptors, interleukin 2 receptor, prostate specific membrane antigen, αβ3 integrin receptor, gastrin-releasing peptide, chemokine receptor 4, and urokinase-type plasminogen receptor, are well established tools for targeted molecular imaging ortumor receptor imaging. Low molecular weight peptides allow a rapid clearance from the blood and result in favorable target-to-non-target ratios. It also displays a good tissue penetration and non-immunogenicity. The only drawback of using peptides is their potential low metabolic stability. In this review article, we have discussed and evaluated the role of peptides in imaging and non-imaging diagnostics. The most popular non-imaging and imaging diagnostic platforms are discussed, categorized, and ranked, as per their scientific contribution on PUBMED. Moreover, the applicability of peptide-based diagnostics in deadly diseases, mainly COVID-19 and cancer, is also discussed in detail.

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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

Cited by 47 publications

References 51 publications

PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook

PSMA PET Imaging in Glioblastoma: A Preclinical Evaluation and Theranostic Outlook

Prostate-Specific Membrane Antigen in Anaplastic and Poorly Differentiated Thyroid Cancer—A New Diagnostic and Therapeutic Target?

Role of Peptides in Diagnostics

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