Radiopharmaceuticals: new antimicrobial agents.

Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Trends in Biotechnology (Impact Factor: 9.66). 03/2003; 21(2):70-3. DOI: 10.1016/S0167-7799(02)00032-X
Source: PubMed

ABSTRACT Small antimicrobial peptides are good candidates for new antimicrobial agents. A scintigraphic approach to studying the pharmacokinetics of antimicrobial peptides in animals has been developed. The peptides were safely and reproducibly labelled with technetium-99m and, after intravenous injection of the radiolabelled peptides into infected animals, scintigraphy allowed real-time quantification of the peptide in the various body compartments. Antimicrobial peptides rapidly accumulated at sites of infection but not at sites of sterile inflammation, indicating that radiolabelled antimicrobial peptides could be used in detection of infection. These radiopharmaceuticals enabled the efficacy of antibacterial therapy in animals to be monitored. The scintigraphic approach provides a useful method for investigating the pharmacokinetics of small peptides in animals.

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    ABSTRACT: Ubiquicidin (UBI) 29-41 is a cationic, synthetic antimicrobial peptide fragment that binds preferentially with the anionic microbial cell membrane at the site of infection. The current study was conducted to evaluate its potential as an infection-imaging agent in humans. Eighteen patients, 9 female and 9 male (mean age, 31.7 y; range, 5-75 y), with suspected bone, soft-tissue, or prosthesis infections were included in the study. (99m)Tc-UBI 29-41 in a dose of 400 microg/370-400 MBq was injected intravenously in adults. A dynamic study was followed by spot views of the suspected region of infection (target) and a corresponding normal area (nontarget) at 30, 60, 120, and 240 min. The target-to-nontarget ratios were used to find the optimum time for imaging. Whole-body anterior and posterior images were also acquired at 30, 120, and 240 min to study biodistribution. Activity in each organ was expressed as percentage retained dose. Visual score (0-3) was used to categorize studies as positive or negative, with scores of 0 (minimal or no uptake; equivalent to soft tissue) and 1 (mild; less uptake than in liver) being considered negative and scores of 2 (moderate; uptake greater than or equal to that in liver) and 3 (intense; uptake greater than or equal to that in kidneys) being considered positive. Scans were interpreted as true- or false-positive and true- or false-negative on the basis of bacterial culture as the major criterion and the results of clinical tests, radiography, and 3-phase bone scanning as minor criteria. The biodistribution study showed a gradual decline in renal activity as percentage of administered dose from 6.53% +/- 0.58% at 30 min to 4.54% +/- 0.57% at 120 min and 3.38% +/- 0.55% at 240 min. The liver showed a similar trend, with values of 5.43% +/- 0.76%, 3.17% +/- 0.25%, and 2.02% +/- 0.30% at 30, 120, and 240 min, respectively. Radioactivity accumulated gradually in the urinary bladder, with values of 4.60% +/- 0.92% at 30 min, 23.00% +/- 2.32% at 120 min, and 38.85% +/- 4.01% at 240 min. Of 18 studies performed with 99mTc-UBI 29-41, 14 showed positive findings and 4 showed negative findings. Negative findings were subsequently confirmed to be true negative. The positive findings for 1 scan were interpreted as false positive, as no growth was obtained on bacterial culture and no evidence of infection was found on minor criteria. In 10 cases, the major criterion was used, whereas in 4 cases minor criteria had to be used for interpretation. Quantitative analysis revealed a maximum mean target-to-nontarget ratio of 2.75 +/- 1.69 at 30 min, which decreased to 2.04 +/- 1.01 at 120 min. The overall sensitivity, specificity, and accuracy were 100%, 80%, and 94.4%, respectively. No adverse reactions were observed during image acquisition and within 5 d after the study. 99mTc-UBI 29-41 showed promise in localizing foci of infection, with optimal visualization at 30 min.
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    ABSTRACT: Cerebral aggregation of amyloid-β (Aβ) is thought to play a major role in the etiology of Alzheimer's disease. Environmental influences, including chronic bacterial or viral infections, are thought to alter the permeability of the blood-brain barrier (BBB) and thereby facilitate cerebral colonization by opportunistic pathogens. This may eventually trigger Aβ overproduction and aggregation. Host biomolecules that target and combat these pathogens, for instance, antimicrobial peptides (AMPs) such as Aβ itself, are an interesting option for the detection and diagnostic follow-up of such cerebral infections. As part of the innate immune system, AMPs are defensive peptides that efficiently penetrate infected cells and tissues beyond many endothelial barriers, most linings, including the BBB, and overall specifically target pathogens. Based on existing literature, we postulate a role for labeled AMPs as a marker to target pathogens that play a role in the aggregation of amyloid in the brain.
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    ABSTRACT: PURPOSE: Detection of osteomyelitis beneath a diabetic foot ulcer is imperative for proper management; however, accurate and noninvasive diagnosis of osteomyelitis remains a challenge. Ubiquicidin 29-41 (UBI 29-41) is a synthetic antimicrobial peptide fragment reported to be highly infection-specific. (99m)Tc-UBI 29-41 has recently been reported to be a promising radiotracer for infection imaging. The aim of this prospective study was to evaluate the utility of (99m)Tc-UBI 29-41 scintigraphy in diabetic patients with suspected osteomyelitis of the foot. METHODS: Included in the study were 65 patients with type 2 diabetes mellitus and foot ulcer and with clinical suspicion of osteomyelitis . Each patient had a three-phase bone scan and a (99m)Tc-UBI scan at 30 and 60 min after injection. The scan was considered to be consistent with osteomyelitis when the (99m)Tc-UBI 29-41 uptake was concordant with the (99m)Tc-MDP uptake. It was considered negative for osteomyelitis if there was no uptake of (99m)Tc-UBI 29-41 or if (99m)Tc-UBI 29-41 accumulated in an area not concordant with the abnormal uptake of (99m)Tc-MDP on the bone scan. In the latter case a diagnosis of soft-tissue infection was made. Bone infection was confirmed by bone biopsy/culture and by clinical and radiological follow-up. RESULTS: Final analysis was done in 55 patients. Osteomyelitis was confirmed in 37 patients, and 18 patients were free of bone infection. (99m)Tc-UBI 29-41 was positive in all 37 patients and with the bone scan as the reference for the bone identified all osteomyelitic foci (68 in total). (99m)Tc-UBI 29-41 was negative for osteomyelitis in all 18 patients, and 17 of these patients were diagnosed with soft-tissue infection ((99m)Tc-UBI 29-41 accumulation without concordant abnormal uptake on bone scintigraphy). The sensitivity, specificity and accuracy of (99m)Tc-UBI 29-41 scan in combination with three-phase bone scan for the diagnosis of osteomyelitis in diabetic foot was 100 %. Accuracy for soft-tissue infection was also 100 %. Maximum accumulation of the (99m)Tc-UBI 29-41 with maximum target to background activity was observed in the infectious foci at 30 min after injection. CONCLUSION: Tc-UBI 29-41 may be a useful agent for the accurate diagnosis of bone infection in diabetic foot because of the high accuracy demonstrated in this pilot study. It was able to differentiate between bone and soft-tissue involvement effectively in combination with a bone scan.
    European Journal of Nuclear Medicine 01/2013; · 4.53 Impact Factor

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