Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA.
Curr Mol Med. 2012 May;12(4):458-66. doi: 10.2174/156652412800163361.
Previous studies have demonstrated the feasibility of translocator protein (TSPO) imaging to visualize and quantify human breast adenocarcinoma (MDA-MB-231) cells in vivo using a TSPO-targeted near-infrared (NIR) probe (NIR-conPK11195). This study aimed to extend the use of the TSPO-targeted probe to a more biologically relevant and clinically important tumor microenvironment as well as to assess our ability to longitudinally detect the presence and progression of breast cancer cells in the brain. The in vivo biodistribution and accumulation of NIR-conPK11195 and free (unconjugated) NIR dye were quantitatively evaluated in intracranial MDA-MB-231-bearing mice and non-tumor-bearing control mice longitudinally once a week from two to five weeks post-inoculation. The in vivo time-activity curves illustrate distinct clearance profiles for NIR-conPK11195 and free NIR dye, resulting in preferential accumulation of the TSPO-targeted probe in the intracranial tumor bearing hemisphere (TBH) with significant tumor contrast over normal muscle tissue (p < 0.005 at five weeks; p < 0.01 at four weeks). In addition, the TSPO-labeled TBHs demonstrated significant contrast over the TBHs of mice injected with free NIR dye (p < 0.001 at four and five weeks) as well as over the TSPO-labeled non-tumor-bearing hemispheres (NTBHs) of control mice (p < 0.005 at four and five weeks). Overall, TSPO-targeted molecular imaging appears useful for visualizing and quantifying breast cancer xenografts propagated in the murine brain and may assist in preclinical detection, diagnosis and monitoring of metastatic disease as well as drug discovery. Furthermore, these results indicate it should be possible to perform TSPO-imaging of breast cancer cells in the brain using radiolabeled TSPO-targeted agents, particularly in light of the fact that [11C]-labeled TSPO probes such as [11C]-PK 11195 have been successfully used to image gliomas in the clinic.
先前的研究已经证明，使用 TSPO 靶向近红外（NIR）探针（NIR-conPK11195）对活体人乳腺癌 MDA-MB-231 细胞进行可视化和定量是可行的。本研究旨在将 TSPO 靶向探针的用途扩展到更具生物学相关性和临床重要性的肿瘤微环境，并评估我们在大脑中纵向检测乳腺癌细胞存在和进展的能力。在颅内 MDA-MB-231 荷瘤小鼠和非荷瘤对照小鼠中，每周一次，从接种后两周到五周，定量评估 NIR-conPK11195 和游离（未结合）NIR 染料的体内生物分布和积累。体内时间-活性曲线说明了 NIR-conPK11195 和游离 NIR 染料的清除特征明显不同，导致 TSPO 靶向探针优先在颅内肿瘤荷瘤半球（TBH）中积累，与正常肌肉组织有显著的肿瘤对比度（五周时 p < 0.005；四周时 p < 0.01）。此外，TSPO 标记的 TBH 与注射游离 NIR 染料的小鼠的 TBH（四周和五周时 p < 0.001）以及对照小鼠的 TSPO 标记的非肿瘤荷瘤半球（NTBH）相比，具有显著的对比度（四周和五周时 p < 0.005）。总之，TSPO 靶向的分子成像似乎可用于可视化和定量检测在鼠脑中传播的乳腺癌异种移植物，并且可能有助于临床前检测、诊断和监测转移性疾病以及药物发现。此外，这些结果表明，使用放射性标记的 TSPO 靶向剂对脑内乳腺癌细胞进行 TSPO 成像应该是可行的，特别是考虑到[11C]-标记的 TSPO 探针，如[11C]-PK 11195，已经成功地用于临床中的脑胶质瘤成像。
