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Anti-Infective Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5214
ISSN (Online): 1875-6018

Current Status of Imaging Infections with Radiolabeled Anti-Infective Agents

Author(s): Mick M. Welling, Guillermina Ferro-Flores, Ioannis Pirmettis and Carlo P.J.M. Brouwer

Volume 8, Issue 3, 2009

Page: [272 - 287] Pages: 16

DOI: 10.2174/187152109788680180

Price: $65

Abstract

Infection specific radiopharmaceuticals can be used for diagnosis, decision-making in therapy and treatment follow-up. Research has been ongoing to develop infection specific markers since clinically used tracers cannot discriminate between infection and inflammation. A specific radiopharmaceutical for infection imaging should satisfy the following criteria: high and specific uptake at the infection site, rapid infection detection and background clearance, minimal accumulation in non-target tissues, low toxicity, zero immune response and especially the ability to differentiate infection from sterile inflammation. Radiolabeled anti-infective agents can fulfill the majority of these requirements. Technetium- 99m (99mTc) labeled antibiotics have potential to differentiate sterile inflammation from infection. There are numerous studies reporting the use of radiolabeled antibacterial and antifungal agents for infection detection. Other promising agents are antimicrobial peptides (AMPs) since they preferentially bind to bacteria membranes instead of those of mammalian cells thus distinguishing between infection and sterile inflammation. Synthetic AMPs derived from human natural peptides offers possibility for studying the effects of polymerization and substituting the amino acid sequence to design a specific micro-organism seeking tracer. 99mTc-labeled anti-infectives are ideal as infection-seeking agents because of its direct and fast accumulation. Clinical studies already undertaken and further evaluation with different pathogen types such as viruses, fungi, parasites and intracellular pathogens in humans will improve the potential of these compounds. Radiochemical techniques for labeling anti-infectives have been developed to optimize biodistribution and targeting properties of tracers. An important issue is the technetium-99m specific coordination site in the anti-infective molecule and its chemical and biochemical characterization.

Keywords: Antibiotics, antimicrobial peptides, radiolabeling, technetium, infection, scintigraphy

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