Nuclear medicine imaging techniques offer whole body imaging for localization of number and site of infective foci inspite of limitation of spatial resolution. The innate human immune system contains a large member of important elements including antimicrobial peptides to combat any form of infection. However, development of antibiotics against bacteria progressed rapidly and gained popularity over antimicrobial peptides but even powerful antimicrobials failed to reduce morbidity and mortality due to emergence of mutant strains of bacteria resulting in antimicrobial resistance. Differentiation between infection and inflammation using radiolabeled compounds with nuclear medicine techniques has always been a dilemma which is still to be resolved. Starting from nonspecific tracers to specific radiolabeled tracers, the question is still unanswered. Specific radiolabeled tracers included antibiotics and antimicrobial peptides which bind directly to the bacteria for efficient localization with advanced nuclear medicine equipments. However, there are merits and demerits attributed to each. In the current paper, radiolabeled antibiotics and radiolabeled peptides for infection localization have been discussed starting with the background of primitive nonspecific tracers. Radiolabeled antimicrobial peptides have certain merits compared with labeled antibiotics which make them superior agents for localization of infective focus. 1. General Introduction Blood-derived antimicrobial proteins and peptides being part of innate immunity target the microbial membranes leading to growth arrest and, in some instants, neutralization of proinflammatory surface components like lipopolysaccharides. Different inflammatory response blood cells like neutrophils, eosinophils, macrophages, and platelets contain antimicrobial proteins and peptides which have affinity for surface lipids of microbial as opposed to eukaryotic cells. Neutrophils contain primary and secondary granules in their cytoplasm which contain antimicrobial proteins and peptides. Lactoferrin is localized in the secondary granules, which has direct microbicidal effect, presumably via membrane disruption. Activated neutrophils release bactericidal/permeability increasing protein (BPI) into inflammatory fluids where it is potentially bactericidal. Serprocidins are proteases with cytotoxic activity localized in neutrophil primary granules. Cathelicidins are also antimicrobial peptides within secondary granules of neutrophils. The defensins are a family of 4-Kd peptides with broad cytotoxic activity against bacteria,
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