Tyrosinase as a multifunctional reporter gene for Photoacoustic/MRI/PET triple modality molecular imaging

Abstract

Development of reporter genes for multimodality molecular imaging is highly important. In contrast to the conventional strategies which have focused on fusing several reporter genes together to serve as multimodal reporters, human tyrosinase (TYR) – the key enzyme in melanin production – was evaluated in this study as a stand-alone reporter gene for in vitro and in vivo photoacoustic imaging (PAI), magnetic resonance imaging (MRI) and positron emission tomography (PET). Human breast cancer cells MCF-7 transfected with a plasmid that encodes TYR (named as MCF-7-TYR) and non-transfected MCF-7 cells were used as positive and negative controls, respectively. Melanin targeted N-(2-(diethylamino)ethyl)-18F-5-fluoropicolinamide was used as a PET reporter probe. In vivo PAI/MRI/PET imaging studies showed that MCF-7-TYR tumors achieved significant higher signals and tumor-to-background contrasts than those of MCF-7 tumor. Our study demonstrates that TYR gene can be utilized as a multifunctional reporter gene for PAI/MRI/PET both in vitro and in vivo.

Intrastriatal Transplantation of Retinal Pigment Epithelial Cells for the Treatment of Parkinson Disease: In Vivo Longitudinal Molecular Imaging with18F-P3BZA PET/CT

“…It displays high melanin targeting specificity and shows excellent performance for in vivo imaging of melanotic melanoma (21,22). In our study, as expected, 18 F-P3BZA specifically and effectively localizes in pRPE cells in a melanin-dependent manner in vitro and in vivo.…”

“…Details of methods are in Appendix E1 (online). This includes radiosynthesis of 18 F-P3BZA (prepared according to a previously published procedure [21,22]). Melanotic pRPE (23) and amelanotic ARPE-19 cells (24) were used as positive and negative controls, respectively, for evaluating 18 F-P3BZA in vitro and in vivo.…”

In vivo tumor detection with combined MR–Photoacoustic-Thermoacoustic imaging

“…While triple-modality imaging methods utilizing PAT, MRI, and PET or Raman have been reported, [8][9][10][11] to our knowledge, it is the¯rst time that MRI, PAT, and TAT are combined for in vivo cancer detection. In addition to the morphological information obtained by MRI, PAT, and TAT o®er us the possibility to access the optical and microwave absorption functional properties of tumor, which are sensitive to tumor vasculature (optical absorption coe±cient) and water content (e®ective conductivity), respectively.…”

Listen to the chemical and histological information in biological tissue

“…optical mean free path, in most biological tissues is on the order of 1 mm. When beyond this depth, multiple light scattering would quickly randomize the trajectories of incident photons and prevent effective optical focusing in tissue [12][13][14][15]. Therefore, pure optical modalities either suffer from poor spatial resolution or have limited imaging depth [16].…”

“…based on their different optical absorption spectra. The hybrid PAI technology, by combining the advantages of both light and sound, shows tremendous potential applications in medicine and biology, and has already been used in evaluating the anatomical, functional, metabolic, molecular and genetic information of biological samples [12][13][14][15][16][17][18][19][20].…”