Abstract
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Objectives: Prostate-specific membrane antigen (PSMA) is playing a key role in the targeted radionuclide therapy as well as diagnostics in patients with prostate cancer. Recently, the new PSMA ligand [18F]PSMA-1007 was introduced as promising PET tracer to detect PSMA upregulation in small animal PET imaging and clinical PET studies. Our aim was to compare [18F]PSMA-1007 uptake with PSMA immunohistochemical staining using the LNCaP-tumor xenograft model. [Methods] LNCaP (PSMA-positive prostate cancer cell line) was subcutaneously inoculated bilaterally into male SCID mice (n=4). Tumor xenograft mice (body weight 26.3 ± 0.97 g) were investigated using a small animal PET scanner (Siemens Inveon PET/CT) when the tumor size reached 1.13 - 2.78 cm3 (seven tumors in four mice). Static PET images were acquired at 60 min post injection of [18F]PSMA-1007 (19.2 ± 2.3 MBq) under isoflurane anesthesia. After the PET/CT scan, immunohistochemical staining of the tumor was performed using anti-PSMA antibody (ab140348, Abcam). Upregulation levels of PSMA were evaluated using scaled scoring by the visual analysis of the sections (5: very high, 4: high, 3: moderate, 2; low, and 1: minimal). Tumoral uptakes of [18F]PSMA-1007 on PET were compared with histological PSMA upregulation by the Spearman’s test. [Results] PET/CT imaging showed high uptakes of [18F]PSMA-1007 in the LNCaP tumors, especially in the rim region of each tumor (SUVmax = 4.76 ± 1.03 (3.22 - 6.59)). PSMA immunohistochemical analysis showed heterogeneous and marginally-dominant distribution of PSMA-positive cells, which surrounded central necrosis of LNCaP tumors. There was a significant positive correlation between [18F]PSMA-1007 uptakes (SUVmean) on PET and PSMA expression levels on histology (ρ=0.797, p=0.03). [Conclusions] This study showed a significant correlation between the [18F]PSMA-1007 uptake and immunohistolochemical PSMA staining. PSMA upregulation levels can be correctly evaluated using [18F]PSMA-1007 PET as well as the detection of the tumor, suggesting the usefulness for theragnostic targeting PSMA. [Fig.1] Whole-body PET scans as axial, coronal and sagittal view of the tumor xenograft model (0.22mm of slice). Arrow indicates high [18F]PSMA-1007 uptake in the LNCaP tumor. [Fig.2] Microscopic appearance by immunohistochemical staining of PSMA and Hematoxylin and Eosin staining. There are many PSMA-positive cells in the rim region of the tumor. [Fig.3] Comparison between the [18F]PSMA-1007 uptake and the immunohistochemical staining of PSMA. The staining indicates the PSMA-upregulation and tumor necrosis, corresponding to the 18F-PSMA-PET/CT result.