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

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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Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22147431 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7431

Author(s):

Magdalena Staniszewska ◽

Pedro Fragoso Costa ◽

Matthias Eiber ◽

Jasmin M. Klose ◽

Jasmin Wosniack ◽

...

Keyword(s):

Prostate Cancer ◽

Flow Cytometry ◽

Androgen Receptor ◽

Xenograft Model ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Positron Emission ◽

Pet Ct ◽

Pre Treatment ◽

Psma Expression

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of PSMA and androgen receptor (AR) expression on the human PC cell lines 22Rv1, C4-2, and LNCaP by immunohistochemistry and flow cytometry revealed low (22Rv1) and high (C4-2 and LNCaP) PSMA expression, and high, comparable AR positivity. Treatment with enzalutamide increased PSMA levels in 22Rv1, C4-2, and LNCaP (2.2/2.3/2.6-fold, p = 0.0005/0.03/0.046) after one week compared to DMSO-treated controls as assessed by flow cytometry. NOD/Scid mice bearing 22Rv1 tumors were treated with enzalutamide for two weeks. Positron emission tomography/computed tomography (PET/CT) demonstrated higher tumor uptake of 68Ga-PSMA after enzalutamide treatment (p = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of 68Ga-PSMA after enzalutamide on PET/CT and post-therapeutic 177Lu-PSMA scintigraphy in a patient with mCRPC. Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for 177Lu-PSMA RLT.

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Heterogenous PSMA expression in primary tumor of prostate cancer as a reason for negative 68 Ga-PSMA PET/CT scan? Immunohistochemical validation of 40 patients undergoing radical prostatectomy

10.1055/s-0040-1708334 ◽

2020 ◽

Author(s):

W Cytawa ◽

S Kircher ◽

C Lapa ◽

AK Buck ◽

B Brockhuis ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Ct Scan ◽

Primary Tumor ◽

Psma Pet ◽

Pet Ct ◽

Pet Ct Scan ◽

Psma Expression

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Evaluation of a New 99mTc-labeled GnRH Analogue as a Possible Imaging Agent for Prostate Cancer Detection

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200619175352 ◽

2020 ◽

Vol 20 (14) ◽

pp. 1695-1703

Author(s):

Arezou Masteri Farahani ◽

Fariba Maleki ◽

Nourollah Sadeghzadeh ◽

Saeid Abediankenari ◽

Seyed Mohammad Abedi ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Nude Mice ◽

Normal Saline ◽

Radiochemical Purity ◽

Prostate Cancer Cell ◽

Gnrh Analogue ◽

Tumor Uptake ◽

Prostate Cancer Cell Lines

Introduction: Prostate cancer is a serious threat to men’s health so it is necessary to develop technics for early detection of this malignancy. The purpose of this research was the evaluation of a new99mTc-labeled GnRH analogue as an imaging probe for tumor targeting of prostate cancer. Methods: 99mTc-labeled-DLys6-GnRH analogue was prepared based on HYNIC as a chelating agent and tricine/ EDDA as coligands for labeling with 99mTc. HYNIC was coupled to epsilon amino group of DLys6 through aminobutyric acid (GABA) as a linker. Radiochemical purity and stability in normal saline and serum, were determined by TLC and HPLC methods. Furthermore, calculation of protein-binding and partition coefficient constant were carried out for 99mTc labeled peptide. The cellular experiments including receptor binding specificity and affinity were studied using three prostate cancer cell lines LN-CaP, DU-145 and PC-3. Finally, the animal assessment and SPECT imaging of radiolabeled GnRH analogue were evaluated on normal mice and nude mice bearing LN-CaP tumor. Results: The GnRH conjugate was labeled with high radiochemical purity (~97%). The radiolabeled peptide showed efficient stability in the presence of normal saline and human serum. The in vitro cellular assays on three prostate cancer cell lines indicated that the radiotracer was bound to LN-CaP cells with higher affinity compared to DU-145 and PC-3 cells. The Kd values of 99mTc- HYNIC (tricine/ EDDA)-Gaba-D-Lys6GnRH were 89.39±26.71, 93.57±30.49 and107.3±18.82 in LN-CaP, PC-3 and DU-145 cells respectively. The biodistribution studies in normal mice and LN-CaP tumor-bearing nude mice showed similar results including rapid blood clearance and low radioactivity accumulation in non-target organs. High kidney uptake proved that the main excretion route of radiopeptide was through the urinary system. The tumor uptake was 1.72±0.45 %ID/g at 1h p.i. decreasing to 0.70±0.06%ID/g at 4h p.i. for 99mTc-HYNIC-Gaba-D-Lys6GnRH. The maximum tumor/ muscle ratio was 2.30 at 1h p.i. Pre-saturation of receptor using an excess of unlabeled peptide revealed that the tumor uptake was receptor mediated. The results of the SPECT image of LN-CaP tumor were in agreement with the biodistribution data. Conclusion: Based on this study, we suggest LN-CaP as a favorable cell line for in vivo studies on GnRH analogues. Moreover, this report shows that 99mTc-HYNIC (tricine/EDDA)-Gaba-D-Lys6GnRH may be a suitable candidate for further evaluation of prostate cancer.

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The diagnostic value of PET/CT imaging with the 68Ga-labeled PSMA-ligand in the follow up assessment of prostate cancer after therapy

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-020-00259-2 ◽

2020 ◽

Vol 51 (1) ◽

Author(s):

Talaat Ahmed Abd El Hameed Hassan ◽

Mohammed Samy Elazab

Keyword(s):

Prostate Cancer ◽

Diagnostic Value ◽

Ct Imaging ◽

Psma Ligand ◽

Pet Ct

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[18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes

Radiation Oncology ◽

10.1186/1748-717x-6-44 ◽

2011 ◽

Vol 6 (1) ◽

Cited By ~ 77

Author(s):

Florian Würschmidt ◽

Cordula Petersen ◽

Andreas Wahl ◽

Jörg Dahle ◽

Matthias Kretschmer

Keyword(s):

Prostate Cancer ◽

Lymph Nodes ◽

Treatment Planning ◽

Dose Escalation ◽

Radiation Treatment ◽

Ct Imaging ◽

Radiation Treatment Planning ◽

Primary Prostate Cancer ◽

Pet Ct ◽

Positive Lymph Nodes

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40. PET/CT Imaging of PSMA-Targeted Human T-Cells in Systemic Prostate Cancer Model

Molecular Therapy ◽

10.1016/s1525-0016(16)39443-6 ◽

2008 ◽

Vol 16 ◽

pp. S16

Keyword(s):

Prostate Cancer ◽

T Cells ◽

Ct Imaging ◽

Cancer Model ◽

Human T Cells ◽

Pet Ct ◽

Prostate Cancer Model

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The value of intravenous contrast medium in PSMA PET/CT imaging in patients with biochemical recurrence of prostate cancer

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000001453 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Alain Winiger ◽

Maria del Sol Pérez Lago ◽

Dirk Lehnick ◽

Justus E. Roos ◽

Klaus Strobel

Keyword(s):

Prostate Cancer ◽

Contrast Medium ◽

Biochemical Recurrence ◽

Ct Imaging ◽

Intravenous Contrast ◽

Intravenous Contrast Medium ◽

Psma Pet ◽

Pet Ct

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Assessment of the Aging of the Brown Adipose Tissue by 18F-FDG PET/CT Imaging in the Progeria Mouse Model Lmna−/−

Contrast Media & Molecular Imaging ◽

10.1155/2018/8327089 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Zhengjie Wang ◽

Xiaolong Xu ◽

Yi Liu ◽

Yongheng Gao ◽

Fei Kang ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Fdg Pet ◽

Uncoupling Protein ◽

Ct Imaging ◽

Terminal Deoxynucleotidyl Transferase ◽

Expression Levels ◽

Brown Adipose ◽

Pet Ct ◽

Fdg Pet Ct

Brown adipose tissue (BAT) is an important energy metabolic organ that is highly implicated in obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used 18F-FDG PET/CT imaging to assess BAT aging in Lmna−/− mice. The maximum standardized uptake value (SUVMax) of the BAT was measured, and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor (β3-AR), and the PR domain-containing 16 (PRDM16) were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis. Apoptosis and cell senescence rates in the BAT of WT and Lmna−/− mice were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and by CDKN2A/p16INK4a immunohistochemical staining, respectively. At 14 weeks of age, the BAT SUVMax and the expression levels of UCP1, β3-AR, and PRDM16 in Lmna−/− mice were significantly reduced relative to WT mice. At the same time, the number of p16INK4a and TUNEL positively stained cells (%) increased in Lmna−/− mice. Collectively, our results indicate that the aging characteristics and the aging regulatory mechanism in the BAT of Lmna−/− mice can mimic the normal BAT aging process.

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