Biology subjects

Scholl, T. J.

Publications and source records attributed to Scholl, T. J..

3 recordsLinked to original sources

bioRxiv2022

Sensitive Spatiotemporal Tracking of Spontaneous Metastasis in Deep Tissues via a Genetically-Encoded Magnetic Resonance Imaging Reporter

Metastasis remains a poorly understood aspect of cancer biology and the leading cause of cancer-related death, yet most preclinical cancer studies do not examine metastasis, focusing solely on the primary tumor. One major factor contributing to this paradox is a gap in available tools for accurate spatiotemporal measurements of metastatic spread in vivo. Our objective was to develop an imaging reporter system that offers sensitive three-dimensional detection of cancer cells at high resolutions in live mice. We utilized organic anion-transporting polypeptide lb3 (oatp1b3) as a magnetic resonance imaging (MRI) reporter gene to this end, and systematically optimized its framework for in vivo tracking of viable cancer cells in a spontaneous metastasis model. We were able to image metastasis on oatp1b3-MRI at the single lymph node level and continued to track its progression over time as cancer cells spread to multiple lymph nodes and different organ systems in single animals. While initial single lesions were successfully imaged in parallel via bioluminescence, later metastases were obscured by light scatter from the initial node. Importantly, we demonstrate and validate that 100-m isotropic resolution MR images could detect micrometastases in lung tissue estimated to contain fewer than 103 cancer cells. In summary, oatp1b3-MRI enables precise determination of lesion size and location over time and offers a path towards deep-tissue tracking of any oatp1b3-engineered cell type with combined high resolution, high sensitivity, 3D spatial information, and surrounding anatomical context.

bioengineering↗

bioRxiv2021

Gadolinium-free Magnetic Resonance Imaging of the Liver using an Oatp1-targeted Manganese(III) Porphyrin

Controversy surrounding gadolinium-based contrast agents (GBCAs) have rendered their continued utility highly contentious, but the liver-specific GBCA Gd(III) ethoxybenzyl-diethylene triamine pentaacetic acid (Gd(III)-EOB-DTPA) remains in use because it provides unique diagnostic information that could not be obtained by any other means. To address the need for an alternative liver-specific MRI contrast agent, we synthesized Mn(III) 20-(4-ethoxyphenyl) porphyrin-5,10,15-tricarboxylate (Mn(III)TriCP-PhOEt), which exhibited significantly higher r1 relaxivity than Gd(III)-EOB-DTPA, and targeted organic anion-transporting polypeptide 1 (Oatp1) channels as a biomarker of hepatocyte viability. Mn(III)TriCP-PhoEt increased the r1 relaxation rate of cells expressing rodent Oatp1a1 and human Oatp1b3, relative to control cells not expressing these liver channels. In mice, Mn(III)TriCP-PhoEt resulted in significant and specific increases in liver signal intensity on T1-weighted images, and significant decreases in liver T1 time relative to precontrast measurements. Our findings suggest that Mn(III)TriCP-PhOEt operates as a specific and sensitive MR contrast agent for in vivo liver imaging.

biophysics↗

bioRxiv2019

A human photoacoustic imaging reporter gene using the clinical dye indocyanine green.

Photoacoustic imaging (PAI) combines optical contrast with the resolution and depth-detection of ultrasound and is increasingly being utilized for medical imaging in patients. PAI reporter genes would allow for monitoring of cell and gene therapies, but current reporters have immunogenicity and/or toxicity concerns that may limit clinical translation. Here we report a PAI reporter system employing the ability of human organic anion transporting polypeptide 1b3 (Oatp1b3) to take up the clinical dye indocyanine green (ICG) into cells. Following ICG administration, cells synthetically expressing Oatp1b3 exhibited significantly increased PAI signals compared to control cells both in vitro and in mice. Several benefits of this technology are the human derivation of Oatp1b3, and the high extinction coefficient, low quantum yield and pre-existing clinical approval of ICG. We posit that the Oatp1b3-ICG reporter system could be useful for in vivo gene and cell tracking in preclinical and clinical applications.

bioengineering↗