Evaluation of neurotensin receptor 1 as potential biomarker for prostate cancer theranostic use

• Published in: European journal of nuclear medicine and molecular imaging 2019-09, Vol.46 (10), p.2199-2207
• Main Authors: He, Tingting, Wang, Mengzhe, Wang, Hui, Tan, Hongpei, Tang, Yongxiang, Smith, Eric, Wu, Zhanhong, Liao, Weihua, Hu, Shuo, Li, Zibo
• Format: Article
• Language: English
• Subjects: Aged; Androgens; Animal models; Animals; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma - diagnostic imaging; Carcinoma - genetics; Carcinoma - metabolism; Cardiology; Cell Line, Tumor; Fluorine isotopes; Gene expression; Humans; Hyperplasia; Imaging; Immunohistochemistry; Male; Medical imaging; Medical treatment; Medicine; Medicine & Public Health; Metastases; Mice; Middle Aged; Monitoring; Neurotensin; Neurotensin - analogs & derivatives; Neurotensin - metabolism; Neurotensin receptors; Nuclear Medicine; Oncology; Original Article; Orthopedics; Patients; Pets; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Radiology; Radiopharmaceuticals - pharmacokinetics; Receptors; Receptors, Neurotensin - genetics; Receptors, Neurotensin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Staining; Target detection; Theranostic Nanomedicine - methods; Tissues; Tomography; Translational research; Tumors; Xenografts; Xenotransplantation
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-019-04355-y

Introduction Despite recent developments in the diagnosis and treatment of prostate cancer, the advanced stages still have poor survival rates. This warrants further exploration of related molecular targets for patient screening, detection of metastatic disease, and treatment/treatment monitoring. Recent studies have indicated that neurotensin receptors (NTSRs) and their ligand neurotensin (NTS) critically affect the progression of prostate cancers. In this study, we evaluated the expression of neurotensin receptor1 (NTSR1) in patient tissues and performed NTSR1 PET imaging in a prostate cancer animal model. Methods The NTSR1 expression was evaluated in 97 cases of prostate cancer and 100 cases of benign prostatic hyperplasia (BPH) of clinical patients by immunohistochemistry staining. The expression profile of PSMA and GRPR was also performed for comparison. The mRNA expression of NTSR1 in LnCap and PC-3 cells was measured by PCR. NTSR1 PET, and biodistribution studies were performed in PC-3 xenografts using 18 F-DEG-VS-NT. Results NTSR1 showed high or moderate expression in 91.8% of prostate cancer tissue, compared with PSMA (86.7%) and GRPR (65.3%). All examined PSMA-negative tissues showed positive NTSR1 expression, suggesting the potential complementary role of NTSR1 targeted imaging or therapy. Only 8% of BPH shows strong or moderate expression of NTSR1, which is significantly lower than that in prostate cancer (91.8%). PCR results indicated LNCap (an androgen-dependent prostate cancer cell) showed negative NTSR1 expression while PC-3 demonstrated positive expression (an androgen-independent prostate cancer cell), which correlated well with previously reported western blot results. In a preclinical animal model, NTSR1 targeted PET probe 18 F-DEG-VS-NT demonstrated prominent tumor accumulation and low background. Conclusion We have demonstrated that NTSR1 is a promising molecular marker for prostate cancer based on patient tissue staining. The NTSR targeted probe 18 F-DEG-VS-NT demonstrated high tumor to background contrast in animal models, which could be valuable in selecting patients for therapies targeting NTSR1 as well as monitoring therapeutic efficacy during treatment accordingly.