Magnetic Resonance Imaging of PSMA-Positive Prostate Cancer by a Targeted and Activatable Gd(III) MR Contrast Agent
| Autor: | Thomas J. Meade, Hao Li, Jing Wang, Xinning Wang, Dong Luo, James P. Basilion, Chaonan Yuan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
medicine.diagnostic_test Chemistry Mr contrast agent Contrast Media Magnetic resonance imaging General Chemistry urologic and male genital diseases medicine.disease Biochemistry Catalysis Biomarker (cell) Prostate cancer Colloid and Surface Chemistry In vivo medicine Medical imaging Cancer research Ex vivo |
| Zdroj: | Journal of the American Chemical Society. 143:17097-17108 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.1c07377 |
| Popis: | Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed in aggressive prostate cancer (PCa) and has been extensively studied as a PCa diagnostic imaging biomarker. Multiple imaging modalities have exploited PSMA as a biomarker including magnetic resonance (MR), Optical, and PET imaging. Of all the imaging MR imaging provides the most detailed information, concurrently providing anatomical, functional, and potentially molecular information. However, the lower sensitivity of MR requires development of molecular MR contrast agents that provides high signal-to-noise ratios. Herein, we report the first targeted and activatable Gd(III)-based MR contrast agents prostate cancer probe 1 and 2 (PCP-1 and -2). We successfully used PCP-2 to differentiate between PSMA+ and PSMA- prostate cancer cells with both in vitro fluorescence imaging and in vivo MR imaging. The in vivo MR imaging results were further supported by ex vivo fluorescence imaging studies, showcasing the unique bimodal feature of PCP-2. Furthermore, PCP-2 highlights a unique molecular MR probe design strategy that improved the sensitivity of traditional biomarker-targeted MR imaging, addressing a critical unmet need in molecular MR imaging field. This work represents the first example of a targeted and activatable MR contrast agent that can be systemically administered in vivo to highlight PSMA+ prostate tumors, paving the way for the clinical translation of MR PSMA imaging. |
| Databáze: | OpenAIRE |
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