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Synthesis and Preclinical Evaluation of a 68Ga-Radiolabeled Peptide Targeting Very Late Antigen‑3 for PET Imaging of Pancreatic Cancer
journal contribution
posted on 2020-06-30, 11:03 authored by Huiling Li, Lujie Yuan, Yu Long, Hanyi Fang, Mengting Li, Qingyao Liu, Xiaotian Xia, Chunxia Qin, Yongxue Zhang, Xiaoli Lan, Yongkang GaiPancreatic cancer is highly malignant
and has a five-year survival
rate of 5% due to an early lymph node, nerve, and vascular metastasis.
Integrin α3β1 (also called very
late antigen-3, VLA-3) is overexpressed in many tumors and plays a
vital role in tumor formation, recurrence, and metastasis. In this
study, we developed a 68Ga-radiolabeled peptide tracer
targeting the α3 unit of VLA-3 and evaluated its
potential application in positron emission computed tomography (PET)
imaging of pancreatic cancer. NOTA-CK11 was prepared by solid-phase
synthesis and successfully radiolabeled with 68Ga with
greater than 99% radiochemical purity and a specific activity of 37
± 5 MBq/nmol (n = 5). The expression level of
integrin α3 in three human pancreatic cancer cells
was evaluated with the order of SW1990, BXPC-3, and PANC-1 from high
to low, while the expression level of integrin β1 was relatively close. When SW1990 cells with the highest expression
level of VLA-3 were stained with FITC–CK11, strong fluorescence
was observed by flow cytometry and under a laser confocal microscope.
However, no significant fluorescence was observed in the blocking
group when treated with excessive CK11. 68Ga-NOTA-CK11
showed significant radioactivity accumulation in SW1990 cells and
was blocked by CK11 successfully. Subsequent small-animal PET imaging
and biodistribution studies in mice bearing SW1990 xenografts confirmed
its high tumor uptake with a good tumor-to-blood ratio and tumor-to-muscle
ratio (2.45 ± 0.31 and 3.65 ± 0.33, respectively) at 1 h
post injection of the probe. In summary, we successfully developed
a peptide-based imaging agent, 68Ga-NOTA-CK11, that showed
a strong binding affinity with VLA-3 and good target specificity for
SW1990 cells and xenografted pancreatic tumor, rending it a promising
radiotracer for PET imaging of VLA-3 expression in pancreatic cancer.
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68 Ga-Radiolabeled Peptide TargetingCK 11. 68 Ga-NOTA-CK 11FITCSubsequent small-animal PET imaging1 h post injectionα 3 unitlaser confocal microscopepancreatic cancerxenografted pancreatic tumorratioPancreatic Cancer Pancreatic cancerVLA -3 expressionSW 1990 xenograftsexpression levelSW 1990 cellsBXPCmetastasipancreatic cancer cellsIntegrin α 3 β 1peptide-based imaging agentintegrin β 1PANCVLA -3fluorescence68 Ga-radiolabeled peptide tracerintegrin α 3
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