Abstract
Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents.
Highlights
Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health
PETCT and single-photon emission computed tomography (SPECT)-CT instruments are both available as dual imaging systems enabling anatomical computed tomography (3-D Xray) images to be overlaid with the radioactive signal
Positron emission tomography utilizes isotopes with an energetically unstable proton to neutron ratio, which are often produced in a cyclotron or a generator system, where the generator parent isotope may be produced via cyclotron or nuclear reactor
Summary
Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. The design of PET and SPECT tracers capable of imaging enzymatic targets is an enormous challenge due to the need for agents that have high affinity and specificity toward the target enzyme, possess good clearance properties to reduce background signal from nonspecific tissue uptake, and are metabolically stable.
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