Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
PLoS One. 2018 May 24;13(5):e0196998. doi: 10.1371/journal.pone.0196998. eCollection 2018.
Magnetic resonance imaging (MRI) contrast agents (CAs) are chemical compounds that can enhance image contrast on T1- or T2- weighted MR image. We have previously demonstrated the potential of MnCl2, a manganese-based CA, in cellular imaging of breast cancer using T1-weighted MRI. In this work, we examined the potential of another class of manganese-based CAs, manganese porphyrins (MnPs), for sensitive cellular detection of multiple clinical subtypes of breast cancer using quantitative MRI. Using a clinical 3.0-T MRI scanner, the relaxivities of two MnPs, MnTPPS4 and MnTPPS3NH2, and conventional Gd-DTPA (control) were measured in ultrapure water and their T1 contrast enhancement patterns were characterized in multiple clinical subtypes of breast cancer. The toxicity of the three CAs was evaluated in vitro. Compared to Gd-DTPA, both MnTPPS3NH2 and MnTPPS4 enabled a more sensitive multi-subtype detection of four breast cell lines at doses that posed no cytotoxic effects, with MnTPPS3NH2 producing the greatest positive enhancement. The superior T1 enhancement capabilities of MnPs over Gd-DTPA are statistically significant and are likely due to their greater cellular uptake and relaxivities. The results demonstrate that multiple clinical subtypes of breast cancer can be imaged on a 3.0-T MRI scanner using MnPs as T1 cellular CAs.
磁共振成像（MRI）对比剂（CA）是可以增强 T1 或 T2 加权 MRI 图像对比度的化学化合物。我们之前已经证明了 MnCl2（一种基于锰的 CA）在使用 T1 加权 MRI 对乳腺癌进行细胞成像中的潜力。在这项工作中，我们使用定量 MRI 检查了另一类基于锰的 CA，锰卟啉（MnP），用于敏感检测多种临床亚型乳腺癌的潜力。使用临床 3.0-T MRI 扫描仪，在超纯水中测量了两种 MnP（MnTPPS4 和 MnTPPS3NH2）和常规 Gd-DTPA（对照）的弛豫率，并在多种临床亚型乳腺癌中表征了它们的 T1 对比增强模式。在体外评估了三种 CA 的毒性。与 Gd-DTPA 相比，两种 MnTPPS3NH2 和 MnTPPS4 都能够以不产生细胞毒性作用的剂量更敏感地检测四种乳腺癌细胞系的多种亚型，其中 MnTPPS3NH2 产生的正增强最大。MnP 比 Gd-DTPA 具有更高的 T1 增强能力，这在统计学上是显著的，并且可能是由于它们具有更高的细胞摄取率和弛豫率。结果表明，使用 MnP 作为 T1 细胞 CA，多种临床亚型的乳腺癌可以在 3.0-T MRI 扫描仪上成像。
