Development of a Suite of Gadolinium-Free OATP1-Targeted Paramagnetic Probes for Liver MRI.
Sean W McRaeMichael ClearyDaniel DeRocheFrancisco M MartinezYing XiaPeter CaravanEric M GaleJohn A RonaldTimothy J SchollPublished in: Journal of medicinal chemistry (2023)
Five amphiphilic, anionic Mn(II) complexes were synthesized as contrast agents targeted to organic anion transporting polypeptide transporters (OATP) for liver magnetic resonance imaging (MRI). The Mn(II) complexes are synthesized in three steps, each from the commercially available trans -1,2-diaminocyclohexane- N , N , N ', N '-tetraacetic acid (CDTA) chelator, with T 1 -relaxivity of complexes ranging between 2.3 and 3.0 mM -1 s -1 in phosphate buffered saline at an applied field strength of 3.0 T. Pharmacokinetics were assessed in female BALB/c mice by acquiring T 1 -weighted images dynamically for 70 min after agent administration and determining contrast enhancement and washout in various organs. Uptake of Mn(II) complexes in human OATPs was investigated through in vitro assays using MDA-MB-231 cells engineered to express either OATP1B1 or OATP1B3 isoforms. Our study introduces a new class of Mn-based OATP-targeted contrast that can be broadly tuned via simple synthetic protocols.
Keyphrases
- contrast enhanced
- magnetic resonance imaging
- magnetic resonance
- computed tomography
- diffusion weighted imaging
- room temperature
- cancer therapy
- transition metal
- cell cycle arrest
- endothelial cells
- metal organic framework
- induced apoptosis
- deep learning
- machine learning
- high throughput
- type diabetes
- ionic liquid
- drug delivery
- adipose tissue
- skeletal muscle
- cell proliferation
- high fat diet induced
- photodynamic therapy
- single cell
- metabolic syndrome