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 - 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 -