Molecular imaging offers various radiopharmaceuticals for the infection imaging, such as antimicrobial peptides, leukocytes, cytokines, antibiotics, sugars and so on. They present both advantages and disadvantages, however none of them are proved to be highly specific for bacteria. Various factors, including the number and strain of bacteria, the infection site, and the host condition may affect the specificity of tested radiopharmaceuticals. Therefore, there is an open debate regarding the wide variety of radiolabelled compounds for imaging bacteria, and this is the reason why researchers want to find a consensus on the most relevant steps that should be fulfilled when testing a new probe.

In this chapter, general principles of bacterial infection, sterile inflammation and the pathogenesis that lead to the disease will be discussed. In addition, topics regarding the role of nuclear medicine for the differential diagnosis between infection and sterile inflammation will be explained by utilizing a list of clinical application models of radiopharmaceuticals. In particular, there will be a section dedicated to positron emission tomography (PET) imaging, i.e., radionuclides used to label molecules (such as antimicrobial peptides, antibiotics, cells, nanoparticles), their adequate chelating agents and radiolabeling procedures.

A critical issue in developing a new radiopharmaceutical is to not change the native/active conformation of the peptide, its binding activity or its antimicrobic potential, and to make the radiolabeling complex stable in plasma and in blood.

PET radiopharmaceutical is fast evolving search field striving for developing improved imaging agents, especially in terms of distinguishing infection from sterile inflammation. A pathology-specific radiopharmaceutical would definitely improve the quality of life of those patients who suffer of post-surgery infections and would benefit from a new “targeted-medicine” era.