Tumor uptake in glioblastoma multiforme after IV injection of [177Lu]Lu-PSMA-617

Kunikowska, Jolanta; Charzyńska, Ingeborga; Kulinski, Radoslaw; Pawlak, Dariusz; Maurin, Michał; Królicki, Leszek

doi:10.1007/s00259-020-04715-z

Cited by 37 publications

(37 citation statements)

References 6 publications

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“…The most intriguing perspective of PSMA expression in glioblastoma lies in the concept of PSMA-targeted theranostics. PSMA radioligand therapy yields highly satisfactory results in patients with metastatic castration-resistant prostate cancer owing to its high response rates, low toxic effects, and reduction of pain ( 46 ) and a pivotal dosimetry case study of 177 Lu-PSMA-617 treatment in a glioblastoma patient has shown promising preliminary results for the implementation of PSMA radioligand therapy in neuro-oncology as well ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Bearing this in mind, we conclude that salivary gland cancer, glioblastoma, thyroid cancer (differentiated and medullary), hepatocellular carcinoma, and renal cell cancer (clear cell) are the most relevant tumors to further explore the potential of PSMA-RLT. In line with this, the first case reports on PSMA-RLT in patients other than prostate cancer included salivary gland cancer, glioblastoma, thyroid cancer, and hepatocellular carcinoma [30,34,53,55,76,77,102]. These nine heavily pretreated end-stage patients received 1-2 cycles of 5.9-8.4 GBq [ 177 Lu]Lu-PSMA per cycle in compassionate use programs (Table 2).…”

Section: Discussionmentioning

confidence: 87%

PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

Uijen¹,

Derks

Merkx³

et al. 2021

Eur J Nucl Med Mol Imaging

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In the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [177Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.

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“…However, it has been suggested that the uptake of radiolabeled compounds by the microvascular endothelium (and not by tumor cells) may not be optimal (i.e., characterized by a quick washout). Despite this, recent pioneering dosimetry data of [ 177 Lu]Lu-PSMA-617 treatment in other tumors with angiogenesis-associated PSMA expression (e.g., glioblastoma multiforme) has proven the possibility of such targeted treatment, without quick washout of radiolabeled compounds [ 23 ]. Moreover, in HCC, we found most extrahepatic metastatic sites (except bone) showed a higher uptake of tracer than the liver (with a TLR of 3.6 ± 2.1), indicating [ 177 Lu]Lu-PSMA-617 may be a useful treatment.…”

Section: Discussionmentioning

confidence: 99%

[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma

Kunikowska

Cieślak

Gierej

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [ 68 Ga]Ga-PSMA-11 in HCC and its impact on patient management. Methods Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, singleinstitution study. All patients underwent contrast-enhanced MRI/CT, [ 68 Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions. Results No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [ 68 Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUV max) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [ 68 Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC. Conclusion [ 68 Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

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Tumor uptake in glioblastoma multiforme after IV injection of [177Lu]Lu-PSMA-617

Cited by 37 publications

References 6 publications

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

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

PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma

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