Radiopharmaceutical chemistry for positron emission tomography

Molecular imaging is an emerging technology that allows the visualization of interactions between molecular probes and biological targets. Molecules that either direct or are subject to homeostatic controls in biological systems could be labeled with the appropriate radioisotopes for the quantitative measurement of selected molecular interactions during normal tissue homeostasis and again after perturbations of the normal state. In particular, positron emission tomography (PET) offers picomolar sensitivity and is a fully translational technique that requires specific probes radiolabeled with a usually short-lived positron-emitting radionuclide. PET has provided the capability of measuring biological processes at the molecular and metabolic levels in vivo by the detection of the gamma rays formed as a result of the annihilation of the positrons emitted. Despite the great wealth of information that such probes can provide, the potential of PET strongly depends on the availability of suitable PET radiotracers. However, the development of new imaging probes for PET is far from trivial and radiochemistry is a major limiting factor for the field of PET. In this review, we provided an overview of the most common chemical approaches for the synthesis of PET-labeled molecules and highlighted the most recent developments and trends. The discussed PET radionuclides include ¹¹C (t_1/2 = 20.4 min), ¹³N (t_1/2 = 9.9 min), ¹⁵O (t_1/2 = 2 min), ⁶⁸Ga (t_1/2 = 68 min), ¹⁸F (t_1/2 = 109.8 min), ⁶⁴Cu (t_1/2 = 12.7 h), and ¹²⁴I (t_1/2 = 4.12 d).