Multivariate metal-organic frameworks enable chemical shift-encoded MRI with femtomolar sensitivity for biological systems

Fluorescent molecules with speci c target moieties are essential for histo-
pathological analysis, but their limited tissue penetration depth makes in vivo,
in situ color encoding analysis challenging. Magnetic resonance imaging (MRI)
offers deep tissue penetration. When combined with chemical shift-encoded
MRI reporters, it enables in vivo chemical shift encoding for biotarget imaging
and analysis. These reporters require both strong signal intensity and large
chemical shift window. However, conventional proton MRI reporters, with low
sensitivity and a small chemical shift window, limit their in vivo applications.
Here, we describe a chemical shift-encoded hyperpolarized 129Xe MRI reporter
based on the multivariate metal-organic framework, NiZn-ZIF-8, to overcome
these challenges. The proposed NiZn-ZIF-8 gives distinct chemical shifts for
dissolved and entrapped 129Xe without signal interference, enhancing the 129Xe
NMR signal by 210 times compared to dissolved 129Xe in water and biological
media. This enables detection threshold at ≈ 4 fM concentrations, setting a
record for the lowest concentration of xenon hosts detected in nanomaterials.
Additionally, NiZn-ZIF-8 exhibits good in vivo MRI performance, allowing
xenon encoding and distinction in rat lungs. NiZn-ZIF-8 represents a versatile
and powerful platform for advanced molecular imaging and in vivo biomedical
diagnostics.