Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer

Gorges, Tobias M.; Riethdorf, Sabine; Ahsen, Oliver von; Nastały, Paulina; Röck, Katharina; Boede, Marcel; Peine, Sven; Kuske, Andra; Schmid, Elke; Kneip, Christoph; König, Frank; Rudolph, Marion; Pantel, Klaus

doi:10.18632/oncotarget.9004

Cited by 78 publications

(57 citation statements)

References 27 publications

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“…“Liquid biopsy” on circulating tumor cells (CTC) characterization has been studied to address the question of PSMA-targeted therapeutic decision [ 25 ]. But PSMA profiling is not only determined by the cell line.…”

Section: Discussionmentioning

confidence: 99%

Preparation of ⁶⁸Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression

Wang

Shao

et al. 2018

Contrast Media & Molecular Imaging

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Objective To synthesize 68Ga-Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) with a synthesis module and investigate PET-CT imaging to monitor PSMA expression during prostate cancer (PCa) progression and tumor growth in mice bearing subcutaneous PCa xenografts. Method The radiochemical purity and stability of 68Ga-PSMA-11 were determined via radio-HPLC. The PCa cell lines of different PSMA expression levels (PC3, VCAP±, CWR22RV1+, and LNCaP++) were selected to mimic the PCa progression. 68Ga-PSMA-11 biodistribution was studied by dissection method and in vivo imaging with micro PET-CT. The expression levels of PSMA in tumor cells and tissues were analyzed by immunofluorescence, flow cytometry, and western blot. The correlation between PSMA expression and radio-uptake was also evaluated. 2-PMPA preadministration served as a block group. Results The radiochemical purity of 68Ga-PSMA-11 was 99.6 ± 0.1% and stable in vitro for 2 h. The equilibrium binding constant (Kd) of 68Ga-PSMA-11 to LNCaP, CWR22Rv1, PC-3, and VCAP cells was 4.3 ± 0.8 nM, 16.4 ± 1.3 nM, 225.3 ± 20.8 nM, and 125.6 ± 13.1 nM, respectively. Results of tumor uptake (% ID and % ID/g or % ID/cm3) of 68Ga-PSMA-11 in biodistribution and micro PET imaging were LNCaP > CWR22RV1 > PC-3 and VCAP due to different PSMA expression levels. It was confirmed by flow cytometry, western blot, and immunofluorescence. Tumor uptake (% ID/cm3) of 68Ga-PSMA-11 increased with the tumor anatomical volume in quadratic polynomial fashion and reached the peak (when tumor volume was 0.5 cm3) earlier than tumor uptake (% ID). Tumor uptake (% ID/cm3) of 68Ga-PSMA-11 based on functional volume correlated well with the PSMA expression in a linear manner (y = 9.35x + 2.59, R2 = 0.8924, and p < 0.0001); however, low dose 2-PMPA causes rapid renal clearance of increased tumor/kidney uptake of 68Ga-PSMA-11. Conclusions The 68Ga-PSMA-11 PET-CT imaging could invasively evaluate PSMA expression during PCa progression and tumor growth with % ID/cm3 (based on functional volume) as an important index. Low dose 2-PMPA preadministration might be a choice to decrease kidney uptake of 68Ga-PSMA-11.

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Section: Discussionmentioning

confidence: 99%

Preparation of ⁶⁸Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression

Wang

Shao

et al. 2018

Contrast Media & Molecular Imaging

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“…PSMA is a 100 KDa type II membrane protein expressed in all forms of prostate tissues, including prostate carcinoma [32,33]. Therefore, we assessed these markers in our BPH patients to evaluate the possible progression of disease.…”

Section: Discussionmentioning

confidence: 99%

Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study

Morgia

Micali

Rinaldi

et al. 2017

IJMS

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Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated that Serenoa repens (Ser) with lycopene (Ly) and selenium (Se) reawakened apoptosis by reducing survivin and neuronal apoptosis inhibitory protein (NAIP) levels in rats. The aim of this study was to evaluate the effectiveness of Ser-Se-Ly association on survivin and NAIP expression in BPH patients. Ninety patients with lower urinary tract symptoms (LUTS) due to clinical BPH were included in this randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive placebo (Group BPH + placebo, n = 45) or Ser-Se-Ly association (Group BPH + Ser-Se-Ly; n = 45) for 3 months. At time 0, all patients underwent prostatic biopsies. After 3 months of treatment, they underwent prostatic re-biopsy and specimens were collected for molecular, morphological, and immunohistochemical analysis. After 3 months, survivin and NAIP were significantly decreased, while caspase-3 was significantly increased in BPH patients treated with Ser-Se-Ly when compared with the other group. In BPH patients treated with Ser-Se-Ly for 3 months, the glandular epithelium was formed by a single layer of cuboidal cells. PSA showed high immunoexpression in all BPH patients and a focal positivity in Ser-Se-Ly treated patients after 3 months. Evident prostate specific membrane antigen (PSMA) immunoexpression was shown in all BPH patients, while no positivity was present after Ser-Se-Ly administration. Ser-Se-Ly proved to be effective in promoting apoptosis in BPH patients.

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“…Despite the intrinsic limitation that CTCs are rare, 10 analysis of CTCs has allowed a non-invasive, real-time molecular characterization of cancer in patients with metastatic disease 11 , 12 and has successfully been used to predict response to Docetaxel and Prednisone in patients with metastatic castration resistant PC (mCRPC). 13 Additionally, nuclear expression of the androgen receptor variant V7 (AR-V7) in CTCs seems to report response to taxanes.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed?

Minciacchi

Zijlstra

Rubin

et al. 2017

Prostate Cancer Prostatic Dis

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Background:Extracellular vesicles (EVs) are a heterogeneous class of lipid bound particles shed by any cell in the body in physiological and pathological conditions. EVs play critical functions in intercellular communication. EVs can actively travel in intercellular matrices and eventually reach the circulation. They can also be released directly in biological fluids where they appear to be stable. Because the molecular content of EVs reflects the composition of the cell of origin, they have recently emerged as a promising source of biomarkers in a number of diseases. EV analysis is particularly attractive in cancer patients that frequently present with increased numbers of circulating EVs.Methods:We sought to review the current literature on the molecular profile of prostate cancer-derived EVs in model systems and patient biological fluids in an attempt to draw some practical and universal conclusions on the use of EVs as a tool for liquid biopsy in clinical specimens.Results:We discuss advantages and limitations of EV-based liquid biopsy approaches summarizing salient studies on protein, DNA and RNA. Several candidate biomarkers have been identified so far but these results are difficult to apply to the clinic. However, the field is rapidly moving toward the implementation of novel tools to isolate cancer-specific EVs that are free of benign EVs and extra-vesicular contaminants. This can be achieved by identifying markers that are exquisitely present in tumor cell-derived EVs. An important contribution might also derive from a better understanding of EV types that may play specific functions in tumor progression and that may be a source of cancer-specific markers.Conclusions:EV analysis holds strong promises for the development of non-invasive biomarkers in patients with prostate cancer. Implementation of modern methods for EV isolation and characterization will enable to interrogate circulating EVs in vivo.

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Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer

Cited by 78 publications

References 27 publications

Preparation of ⁶⁸Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression

Preparation of ⁶⁸Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression

Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study

Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed?

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Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer

Cited by 78 publications

References 27 publications

Preparation of 68Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression

Preparation of 68Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression

Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study

Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed?

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Preparation of ⁶⁸Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression

Preparation of ⁶⁸Ga-PSMA-11 with a Synthesis Module for Micro PET-CT Imaging of PSMA Expression during Prostate Cancer Progression