Abstract
Here, we report that it’s feasible for imaging gastric adenocarcinoma mice model with prostate-specific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric adenocarcinoma. DKFZ-PSMA-617, a PSMA targeting ligand reported recently, was chosen to be radio-labeled with nuclide 64Cu. 64Cu-PSMA-617 was radio-synthesized in high radio-chemical yield and specific activity up to 19.3 GBq/µmol. It showed good stability in vitro. The specificity of 64Cu-PSMA-617 was confirmed by cell uptake experiments in PSMA (+) LNCaP cell and PSMA (-) PC-3 and gastric adenocarcinoma BGC-823 cells. Micro-PET imaging in BGC-823 and PC-3 xenografts nude mice was evaluated (n = 4). And the tumors were visualized and better tumor-to-background achieved till 24 h. Co-administration of N- [[[(1S)-1-Carboxy-3-methylbutyl]amino]-carbonyl]-L-glutamic acid (ZJ-43) can substantially block the uptake in those tumors. Dissected tumor tissues were analyzed by auto-radiography and immunohistochemistry, and these results confirmed the PSMA expression in neo-vasculature which explained the target molecular imaging of 64Cu-PSMA-617. All those results suggested 64Cu-PSMA-617 may serve as a novel radio-tracer for tumor imaging more than prostate cancer.
Highlights
Gastric cancer is the third most common cause of cancer-related death making up 9% of all the cases [1]
Limitations exist in clinical available methods, such as endoscopic ultrasound (EUS), computed tomography (CT) and magnetic resonance imaging (MRI) [7], for accurately staging the disease, detecting metastatic lesions and monitoring recurrence after radical treatment. 18F-Fluorodeoxyglucose (18F-FDG), which has been generally applied for tumor detection with positron emission tomography (PET) [8], was reported with limited sensitivity and specificity for gastric cancer detection [9, 10]
We demonstrate it is feasible to detect gastric adenocarcinoma in the xenograft BGC-823 tumor model by 64Cu-prostate-specific membrane antigen (PSMA)-617 PET imaging
Summary
Gastric cancer is the third most common cause of cancer-related death making up 9% of all the cases [1]. Complete resection can achieve permanent control when the disease is at early stage, but due to its limited clinical symptom, over 80% of patients are initially diagnosed with advanced cancer with poor prognosis [5, 6]. Limitations exist in clinical available methods, such as endoscopic ultrasound (EUS), computed tomography (CT) and magnetic resonance imaging (MRI) [7], for accurately staging the disease, detecting metastatic lesions and monitoring recurrence after radical treatment. 18F-Fluorodeoxyglucose (18F-FDG), which has been generally applied for tumor detection with positron emission tomography (PET) [8], was reported with limited sensitivity and specificity for gastric cancer detection [9, 10]. We report that it’s feasible to image gastric adenocarcinoma with prostatespecific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric cancer
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