Drug discovery and medical diagnostics have many uses for probes that induce selective, sensitive, and detectable signals with high signal-to-noise ratios in response to the activity of specific enzymes. Although many fluorescent switching probes for enzyme-activity detection exist, they are rarely suitable for in vivo imaging owing to the limited transmission and extensive scattering of light in animals.

Despite being one of the most powerful noninvasive visualization techniques, MRI strategies for high-contrast detection of specific enzyme activities are limited. ¹⁹F MRI shows particular promise because of the high NMR sensitivity of ¹⁹F and lack of background signals, even in vivo, but low sensitivity and poor probe-delivery efficiency currently hinder its development.

Itaru Hamachi and co-workers, Kyoto University, Japan, have designed and synthesized self-assembling ¹⁹F NMR/MRI probes of which the signal can be amplified. Without the activity of a specific enzyme, the probes aggregate and no signal is seen by NMR spectroscopy. However, specific enzymatic activity catalytically cleaves a bond within the probe causing the disassembly of the aggregates and producing NMR-active species. Two probes were used to detect the activity of different enzymes and imaging of the activity of an endogenously secreted enzyme within tumor cells was accomplished.

The simple principle behind this technique should be applicable to various target enzymes by replacing the substrate section of the probe with the appropriate substrate for other target enzymes.

• Specific Detection and Imaging of Enzyme Activity by Signal-Amplifiable Self-Assembling ¹⁹F MRI Probes,
  Kazuya Matsuo, Rui Kamada, Keigo Mizusawa, Hirohiko Imai, Yuki Takayama, Michiko Narazaki, Tetsuya Matsuda, Yousuke Takaoka, Itaru Hamachi,
  Chem. Eur. J. 2013
  DOI: 10.1002/chem.201300817