Infections are the most common cause of patient morbidity in hospitals, and noninvasive imaging modalities such as X-ray/computed tomography (CT) or magnetic resonance imaging that are used to detect an infected site(s) in a patient are not able to distinguish between inflammation, tumors, and microbial infections (1). The early detection of infection in a patient can help healthcare providers devise a suitable treatment plan to control and monitor recovery from the disease. 18F-Labeled fluorodeoxy glucose ([18F]-FDG) has often been used with positron emission tomography to detect infections in the clinical setting, but the diagnosis obtained with this radiochemical must be confirmed with CT before any therapy can be initiated (2). Investigators have also used 67Ga-labeled citrate and 111In- or 99mTc-labeled human immunoglobulins and monoclonal antibodies to detect infections; however, these agents show non-specific accumulation in the infected and inflamed areas of the body (3).
Researchers have shown that a thirteen-amino-acid (aa) cationic antimicrobial peptide (AMP) derived from ubiquicidin (UBI; for the aa sequence and other characteristics of UBI, see Brouwer et al. (4)) and radiolabeled directly with 99mTc ([99mTc]-UBI29-41; the aa sequence of UBI29-41 is: Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg) can be used to detect and distinguish infection from inflammation with scintigraphy in animals and humans (5). The mode of action of AMPs has been schematically presented and explained by Brouwer et al. (1). This labeled peptide was demonstrated to be suitable for the visualization of infections in the soft tissues, bone, bone prosthesis, and the spine (6). However, the chemical structure of the directly labeled peptides is not well understood, and the 99mTc labeling of UBI29-41 is assumed to be due to the coordination of the radionuclide with the Lys and Arg7 residues in the peptide sequence as described elsewhere (7). In an effort to clearly define the chemical structure of [99mTc]-UBI29-41, the peptide was radiolabeled with an indirect method as described by Meléndez-Alafort et al. (6). For this, UBI29-41 was first conjugated to a poly(ethyleneglycol) (PEG)–bearing bifunctional metal chelating agent (N-(N-(3-diphenylphosphinopropionyl)glycyl)-S-tritylcysteine (PN2S)) and then labeled with 99mTc ([99mTc]-PEG-PN2S-UBI29-41). The biodistribution and the ability of [99mTc]-PEG-PN2S-UBI29-41 to visualize infection in mice with single-photon emission computed tomography (SPECT) were then compared to that of the directly labeled [99mTc]-UBI29-41 (6).