11C-Labeled Pictilisib (GDC-0941) as a Molecular Tracer Targeting Phosphatidylinositol 3-Kinase (PI3K) for Breast Cancer Imaging. (3rd November 2019)

• Record Type: Journal Article
• Authors: Han, Na; Jiang, Yaqun; Gai, Yongkang; Liu, Qingyao; Yuan, Lujie; Wang, Yichun; Li, Mengting; Zhang, Yongxue; Lan, Xiaoli
• Other Names: Zannetti Antonella Guest Editor.
• Is Part Of: Contrast media & molecular imaging. Volume 2019(2019)
• Publication Date: 2019-11-03
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1155/2019/1760184
• Languages: English
• ISSNs: 1555-4309

Abstract

Abstract : Pictilisib (GDC-0941) is an inhibitor of phosphatidylinositol 3-kinase (PI3K), part of a signaling cascade involved in breast cancer development. The purpose of this study was to evaluate the pharmacokinetics of pictilisib noninvasively by radiolabeling it with 11 C and to assess the usability of the resulting [ 11 C]-pictilisib as a positron-emission tomography (PET) tracer to screen for pictilisib-sensitive tumors. In this study, pictilisib was radiolabeled with [ 11 C]-methyl iodide to obtain 11 C-methylated pictilisib ([ 11 C]-pictilisib) using an automated synthesis module with a high radiolabeling yield. Considerably higher uptake ratios were observed in MCF-7 (PIK3CA mutation, pictilisib-sensitive) cells than those in MDA-MB-231 (PIK3CA wild-type, pictilisib-insensitive) cells at all evaluated time points, indicating good in vitro binding of [ 11 C]-pictilisib. Dynamic micro-PET scans in mice and biodistribution results showed that [ 11 C]-pictilisib was mainly excreted via the hepatobiliary tract into the intestines. MCF-7 xenografts could be clearly visualized on the static micro-PET scans, while MDA-MB-231 tumors could not. Biodistribution results of two xenograft models showed significantly higher uptake and tumor-to-muscle ratios in the MCF-7 xenografts than those in MDA-MB-231 xenografts, exhibiting high in vivo targeting specificity. In conclusion, [ 11 C]-pictilisib was first successfully prepared, and it exhibited good potential to identify pictilisib-sensitive tumors noninvasively, which may have a great impact in the treatment of cancers with an overactive PI3K/Akt/mTOR signal pathway. However, the high activity in hepatobiliary system and intestines needs to be addressed.