Evaluation of neurotensin receptor 1 as potential biomarker for prostate cancer theranostic use
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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.
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 18F-DEG-VS-NT.
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 18F-DEG-VS-NT demonstrated prominent tumor accumulation and low background.
We have demonstrated that NTSR1 is a promising molecular marker for prostate cancer based on patient tissue staining. The NTSR targeted probe 18F-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.
KeywordsNeurotensin receptor Prostate cancer Positron emission tomography (PET) 18F Prostate specific membrane antigen (PSMA)
This work was supported by the National Natural Science Foundation of China (NSFC) (Grant No. 81471689, 91859207, and 81771873) and UNC-Chapel Hill LCCC pilot grant (Wu).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants and tissue samples were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol was approved by the Human Research Ethics Committee of Xiangya Hospital, Central South University. Informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving animals were in accordance with the ethical standards of UNC-CH, and the protocol was approved by the UNC Institutional Animal Care and Use Committee.
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