New approaches for imaging bacteria and neutrophils for detection of occult infections

Inflammatory and infectious diseases represented, still nowadays, a serious and significant cause of morbidity and mortality worldwide. A rapid and accurate diagnosis plays a pivotal role for early therapeutic interventions and to discriminate the infection from an inflammatory condition.
There is a need of a non-invasive strategies to specifically localize bacterial or immune cells in infectious and inflammatory diseases allowing to save time, reduce costs as well as side-effects due to non-appropriate therapy. Nuclear molecular imaging offers a plethora of radiopharmaceuticals for imaging bacteria and immune cells at preclinical level with possible translation to clinics. In this thesis, we present new and updated approaches to image infections as alternatives to currently available radiopharmaceuticals or to be implemented.
Initially, we performed two systematic reviews giving an extensive overview regarding the available radiopharmaceuticals for bacterial imaging and related concerns that limit their use in humans.
In order to overcome these limits, we tested in vitro and in vivo two novel radiopharmaceuticals, the 99mTc-ciprofloxacin dithiocarbamate for the discrimination of infected sites, although did not seem promising, and 99mTc-HYNIC-polymyxin B whose results suggested it for selective diagnosis of Gram-negative infections.
In clinical practice, radiolabelled autologous WBCs are the nuclear medicine gold standard for the diagnosis of infections and inflammatory disorders. In order to improve the procedure, we tested a new chelating agent, (S3CPh)2 (S2CPh)-complex (SSS-complex) that appeared a not valid alternative to 99mTc-HMPAO; secondly, a new sedimentation agent, Gelofusine, that may be considered a suitable substitute of poly(O-2-hydroxyethyl)starch (HES) for WBCs separation.