TY - JOUR
T1 - Validation of sv2a-targeted pet imaging for noninvasive assessment of neuroendocrine differentiation in prostate cancer
AU - Guan, Bing
AU - Zhou, Ning
AU - Wu, Cheng Yang
AU - Li, Songye
AU - Chen, Yu An
AU - Debnath, Sashi
AU - Hofstad, Mia
AU - Ma, Shihong
AU - Raj, Ganesh V.
AU - He, Dalin
AU - Hsieh, Jer Tsong
AU - Huang, Yiyun
AU - Hao, Guiyang
AU - Sun, Xiankai
N1 - Funding Information:
Funding: This research was funded in part by the University of Texas Southwestern Medical Center (Dallas, Texas), the Cancer Prevention and Research Institute of Texas (CPRIT RP1706638), the Prostate Cancer Research Program of the United States Army Medical Research and Materiel Command (W81XWH-19-10363), the Prostate Cancer Foundation via a Challenge Award, the State Scholarship Council of China (201606280277 to B.G.), and the Jack Krohmer Professorship Funds. No other potential conflicts of interest relevant to this article exist.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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 with18F-SynVesT-1. Although18F-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 by18F-SynVesT-1 but not68Ga-PSMA-11 nor68Ga-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.
AB - 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 with18F-SynVesT-1. Although18F-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 by18F-SynVesT-1 but not68Ga-PSMA-11 nor68Ga-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.
KW - F-SynVesT-1
KW - Neuroendocrine differentiation (NED)
KW - Neuroendocrine prostate cancer (NEPC)
KW - Positron emission tomography (PET)
KW - Synaptic vesicle glycoprotein 2 isoform A (SV2A)
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U2 - 10.3390/ijms222313085
DO - 10.3390/ijms222313085
M3 - Article
C2 - 34884893
AN - SCOPUS:85120645334
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 23
M1 - 13085
ER -