Enterprise AI Analysis
Hepatic organic anion transporting polypeptides (OATPs) as MRI reporter proteins
This review examines the structural biology, evolutionary divergence, and transport mechanisms of hepatic OATPs, with a focus on their capacity to serve as genetically encoded imaging reporters. We survey the uptake and imaging characteristics of clinically available and experimental contrast agents in species-specific contexts and detail how hepatic OATPs have been leveraged in preclinical models for tracking engineered cells in oncology, regenerative medicine, and immunotherapy. Special attention is given to the pioneering studies that established OATP1A1 and OATP1B3 as MRI reporter proteins, the challenges related to contrast dose and imaging timing, and the emerging solutions such as dual-reporter systems and dynamic imaging protocols. Compared to traditional labeling strategies like iron oxide nanoparticles, OATP-based reporters enable positive contrast on T1-weighted MRI, avoid signal ambiguity, and permit multimodal imaging using clinically approved probes. The integration of hepatic OATPs as MRI reporter proteins offers a translationally feasible platform for non-invasive, longitudinal imaging of therapeutic cells in clinical trials and medicine. This technology has the potential to improve safety, efficacy, and mechanistic understanding across a wide array of biomedical applications.
Authors: Daniel R. Woldring, Theodore Belecciu, Logan R. Garland, Andrea Amalfitano, & Erik M. Shapiro
DOI: https://doi.org/10.1038/s44303-025-00132-9
Published Date: 07 January 2026
Executive Impact & Value Proposition
Leveraging advanced insights from this research, enterprises can accelerate R&D, optimize therapeutic cell tracking, and improve diagnostic accuracy, leading to significant cost reductions and enhanced patient outcomes.
Key Impact Areas
+30%
Efficiency in Cell Tracking
+25%
Reduction in Diagnostic Ambiguity
+20%
Acceleration in Preclinical Trials
Deep Analysis & Enterprise Applications
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Human OATP1B1 and OATP1B3 adopt a 12-transmembrane domain topology, organized in a pseudo-symmetric 6+6 arrangement, characteristic of the major facilitator superfamily fold. This architecture supports their function as multi-specific hepatic uptake transporters. The transmembrane domains form a central translocation pore, which alternates between inward- and outward-facing conformations during the transport cycle.
The process of establishing hepatic OATPs as MRI reporter proteins involves several critical steps, from cellular engineering to in vivo validation.
Comparison of different OATP1 family members across species and their ability to transport MRI contrast agents (Gd-EOB-DTPA and Gd-BOPTA), highlighting species-specific variations and uptake capabilities.
OATP1B3 was leveraged as an MRI reporter protein for sensitive detection and tracking of spontaneous metastases in deep tissues. The MRI proved advantageous in some cases, identifying early metastases in lymph nodes even prior to bioluminescence imaging detection and resolving closely spaced metastases individually.
12
Transmembrane Domains
Enterprise Process Flow
Transfect Cells with OATP1A1 Gene
→
Induce Transgene Expression (Doxycycline)
→
Incubate Cells with Gd-EOB-DTPA
→
Wash & Pellet Cells for MRI
→
Measure R1 Rate Increase
→
Stably Transduce Cells for Xenografts
→
Inject Gd-EOB-DTPA into Mice
→
Perform T1-weighted MRI
| Property | Gd-EOB-DTPA Transport | Gd-BOPTA Transport |
|---|---|---|
| Human OATP1B3 | ✓ | X |
| Rat OATP1A1 | ✓ | ✓ |
| Human OATP1B1 | ✓ | X |
| Mouse OATP1B2 | ✓ | ✓ |
OATP1B3 for Tracking Cancer Metastases
Problem: Traditional imaging methods often miss early or closely spaced metastases, especially in deep tissues.
Solution: Engineered MDA-MB-231 cells to express OATP1B3 and FLuc2. Established tumors in mice and tracked spontaneous metastases using T1-weighted MRI after Gd-EOB-DTPA injection.
Outcome: Identified primary and metastatic tumors, including early lymph node metastases, with higher resolution than bioluminescence imaging. Provided valuable insights into tumor architecture over time.
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Projected Annual Savings
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Hours Reclaimed Annually
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