The development of positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging continues to grow due to the ability of these techniques to allow the non-invasive in vivo visualisation of biological processes at the molecular and cellular levels. As well as finding application for the diagnosis of disease, these techniques have also been used in the drug discovery process. Crucial to the growth of these techniques is the continued development of molecular probes that can bind to the target biological receptor with high selectivity. This tutorial review describes the use of PET and SPECT for molecular imaging and highlights key strategies for the development of molecular probes for the imaging of both cancer and neurological diseases.

Covering: 1990 to the end of 1998. Previous related review: 1997, 14, 205

A mild and rapid method for the iodination of arenes that utilizes silver(I) triflimide as a catalyst for activation of N-iodosuccinimide has been developed. The transformation was found to be general for a wide range of anisole, aniline, acetanilide, and phenol derivatives and allowed the late-stage iodination of biologically active compounds such as PIMBA, a SPECT imaging agent of breast cancer, and (−)-IBZM, a dopamine D₂ receptor antagonist. The method was also modified for the radioiodination of arenes using a one-pot procedure involving the in situ generation of [¹²⁵I]-N-iodosuccinimide followed by the silver(I)-catalyzed iodination.

D -amino acids are much less common than their l -isomers but are widely distributed in most organisms. Many d -amino acids, including those necessary for bacterial cell wall formation, are synthesized from the corresponding l -isomers by α-amino acid racemases. The important class of pyridoxal phosphate-independent racemases function by an unusual mechanism whose details have been poorly understood. It has been proposed that the stereoinversion involves two active-site cysteine residues acting in concert as a base (thiolate) and an acid (thiol). Although crystallographic structures of several such enzymes are available, with the exception of the recent structures of glutamate racemase from Bacillus subtilis and of proline racemase from Trypanosoma cruzi , the structures either are of inactive forms (e.g., disulfide) or do not allow unambiguous modeling of the substrates in the active sites. Here, we present the crystal structures of diaminopimelate (DAP) epimerase from Haemophilus influenzae with two different isomers of the irreversible inhibitor and substrate mimic aziridino-DAP at 1.35- and 1.70-Å resolution. These structures permit a detailed description of this pyridoxal 5′-phosphate-independent amino acid racemase active site and delineate the electrostatic interactions that control the exquisite substrate selectivity of DAP epimerase. Moreover, the active site shows how deprotonation of the substrates’ nonacidic hydrogen at the α-carbon (pK _a ≈ 29) by a seemingly weakly basic cysteine residue (pK _a ≈ 8–10) is facilitated by interactions with two buried α-helices. Bacterial racemases, including glutamate racemase and DAP epimerase, are potential targets for the development of new agents effective against organisms resistant to conventional antibiotics.