Abstract
Neuroendocrine prostate cancer (NEPC) is an aggressive and lethal variant of prostate cancer (PCa), and it remains a diagnostic challenge. Herein we report our findings of using synaptic vesicle glycoprotein 2 isoform A (SV2A) as a promising marker for positron emission tomography (PET) imaging of neuroendocrine differentiation (NED). The bioinformatic analyses revealed an amplified SV2A gene expression in clinical samples of NEPC versus castration-resistant PCa with adenocarcinoma characteristics (CRPC-Adeno). Importantly, significantly upregulated SV2A protein levels were found in both NEPC cell lines and tumor tissues. PET imaging studies were carried out in NEPC xenograft models with 18F-SynVesT-1. Although 18F-SynVesT-1 is not a cancer imaging agent, it showed a significant uptake level in the SV2A+ tumor (NCI-H660: 0.70 ± 0.14 %ID/g at 50–60 min p.i.). The SV2A blockade resulted in a significant reduction of tumor uptake (0.25 ± 0.03 %ID/g, p = 0.025), indicating the desired SV2A imaging specificity. Moreover, the comparative PET imaging study showed that the DU145 tumors could be clearly visualized by 18F-SynVesT-1 but not 68Ga-PSMA-11 nor 68Ga-DOTATATE, further validating the role of SV2A-targeted imaging for noninvasive assessment of NED in PCa. In conclusion, we demonstrated that SV2A, highly expressed in NEPC, can serve as a promising target for noninvasive imaging evaluation of NED.
Highlights
The 5-year cancer-specific survival rate for patients with clinically localized and regional Prostate cancer (PCa) is nearly 100%, the 5-year cancer-specific survival sharply drops to 31% for metastatic castration-resistant prostate cancer [2]
In search for a target to develop neuroendocrine differentiation (NED)-targeted theranostics, we have found that synaptic vesicle glycoprotein 2 isoform A (SV2A) can serve as a promising candidate
Our bioinformatic analyses were performed on combined data three data sources: Our bioinformatic analyses were performed on from combined froma three sources: recent report by Beltran et al
Summary
Prostate cancer (PCa) remains the second leading cause of deaths across all cancer types in American men [1]. The 5-year cancer-specific survival rate for patients with clinically localized and regional PCa is nearly 100%, the 5-year cancer-specific survival sharply drops to 31% for metastatic castration-resistant prostate cancer (mCRPC) [2]. Classified as neuroendocrine PC (NEPC) [3,4,5], a subset of mCRPC with universal neuroendocrine differentiation (NED) features manifests an even worse prognosis with an overall survival of
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