Citation: Zhe Li, Haozhi Lei, Zhiqiang Ren, Cheng Wang, Qian Xia, Weihong Tan. Enhancing the stability of ⁶⁸Ga-labeled RNA aptamers for pancreatic β-cell and insulinoma imaging through nucleoside modifications[J]. Chinese Chemical Letters, ;2025, 36(10): 110804. doi: 10.1016/j.cclet.2024.110804 shu

Enhancing the stability of ⁶⁸Ga-labeled RNA aptamers for pancreatic β-cell and insulinoma imaging through nucleoside modifications

Zhe Li ^{a, b, 1} ,
Haozhi Lei ^{b, *,} ,
Zhiqiang Ren ^b ,
Cheng Wang ^c ,
Qian Xia ^{b, c, *,} ,
Weihong Tan ^{b, d, e, *,}

a.
School of Life Sciences, Shanghai University, Shanghai 200444, China
b.
Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
c.
Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
d.
The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China
e.
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China

kflhz@mail.ustc.edu.cn

xiaqian@renji.com

tan@hnu.edu.cn

Received Date: 10 October 2024
Revised Date: 24 December 2024
Accepted Date: 25 December 2024
Available Online: 27 January 2025

Figures(4)

Diabetes and insulinoma represent opposing alterations in pancreatic β-cell mass, with diabetes resulting from irreversible β-cells damage and insulinoma arising from abnormal proliferation. Early diagnosis of both conditions necessitates effective β-cell mass detection. Current detection methods are limited in diagnosing each condition individually or lacking timely and accurate detection. Diabetes is typically identified only after significant β-cell loss, while insulinoma can evade conventional imaging due to their small size. Positron emission tomography/computed tomography (PET/CT) imaging, combining anatomical and functional data, enhances diagnostic accuracy but faces challenges in specificity. This study employed two RNA aptamers (m12–3773 and 1–717) modified to enhance RNase resistance and conjugated with ⁶⁸Ga to create ⁶⁸Ga-NOTA-Ap. ⁶⁸Ga-NOTA-Ap was administered to rats with pancreatic β-cell damage and mice with insulinoma to evaluate its ability to image islets, detect changes in pancreatic β-cell mass (BCM), and identify insulinoma. Modified with methoxy and fluoro, RNA aptamers exhibited enhanced stability and RNases resistance while retaining their dissociation constants (K_d). Furthermore, ⁶⁸Ga-NOTA-Ap effectively detected changes of BCM in rats with pancreatic β-cell damage and imaged insulinoma in mice through recognition of abnormal β-cell proliferation by recognizing clusterin and transmembrane p24 trafficking protein 6 (TMED6) on pancreatic β-cell. The developed ⁶⁸Ga-NOTA-Ap shows promise for early screening of diabetes and insulinoma due to its high sensitivity, specificity, and non-invasive nature. It has potential clinical applications for monitoring pancreatic β-cell function and diagnosing insulinoma.
- Diabetes screening,
- Islet damage,
- Insulinoma imaging,
- RNA aptamers,
- PET/CT imaging
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Enhancing the stability of 68Ga-labeled RNA aptamers for pancreatic β-cell and insulinoma imaging through nucleoside modifications

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通讯作者: 陈斌, bchen63@163.com

Enhancing the stability of ⁶⁸Ga-labeled RNA aptamers for pancreatic β-cell and insulinoma imaging through nucleoside modifications