Utility of 99mTc-labelled antimicrobial peptide ubiquicidin (29-41) in the diagnosis of diabetic foot infection.

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.

An imaging analysis of (99m)Tc-UBI (29-41) uptake in S. aureus infected thighs of rabbits on ciprofloxacin treatment.

PURPOSE: The uptake of (99m)Tc-UBI (29-41) was evaluated at sites of bacterial infections in rabbits before and after treatment with ciprofloxacin. METHODS: Staphylococcus aureus susceptible to ciprofloxacin was used to induce a focal infection in each rabbit of group 1 (G1), group 2 (G2), and group 3 (G3) with 2 x 10(4), 2 x 10(6), and 2 x 10(8) colony forming units (CFU), respectively. After 24 h, images of infected thighs (target: T) and contralateral thighs (nontarget: NT) were acquired. Animals then received ciprofloxacin intramuscularly for 5 days followed by imaging on the third and fifth days. The control group 4 (G4) was imaged at days 1, 3, and 5 under the same acquisition parameters. Group 5 (G5) was employed to study biodistribution of the peptide. RESULTS: Increases in (T/NT) ratios in G1, G2, and G3 were observed from 5 min onwards with maximum values at 60 min. G3 revealed the highest accumulation of the peptide. Growth of the same strain of S. aureus on blood agar medium was visualized after fine needle aspiration. After ciprofloxacin treatment, the images for G1-G3 resulted in significantly decreased (P < 0.05) T/NT values on the third and fifth days that correlated with reduction in number of viable bacteria. No significant difference (P < 0.05) in left to right thigh ratios in the control group (G4) was observed. Biodistribution of the peptide showed rapid removal of tracer from circulation through the kidneys. CONCLUSIONS: ( 99m ) Tc-UBI (29-41) accumulation directly correlates with the number of viable bacteria. This infection localization agent can be utilized for monitoring efficacy and duration of antibiotic treatment.

Antimicrobial peptide 99mTc-ubiquicidin 29-41 as human infection-imaging agent: clinical trial.

UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 99mTc-UBI 29-41 showed promise in localizing foci of infection, with optimal visualization at 30 min.

99mTc-labeled antimicrobial peptide ubiquicidin (29-41) accumulates less in Escherichia coli infection than in Staphlococcus aureus infection.

UNLABELLED: 99mTc-Labeled antimicrobial peptide ubiquicidin, (99m)Tc-UBI (29-41) in a freeze-dried kit, was evaluated as a bacterial infection-seeking agent in Staphlococcus aureus- and Escherichia coli-induced infections. METHODS: Thirty-three rabbits were classified in 3 groups. Biodistribution of (99m)Tc-UBI (29-41) was studied in 3 animals (group I). Uptake of peptide was determined by counting radioactivity in anatomically fitted regions drawn over the liver, kidneys, urinary bladder, and whole body and expressed as the percentage uptake per organ. Experimental thigh muscle infection was induced by injecting 2 x 10(8) colony-forming units of live S. aureus or E. coli bacteria into the right thigh muscle in 20 rabbits (group II). Turpentine oil and formalin-killed S. aureus were used for inducing sterile thigh muscle inflammation in 10 rabbits (group III). On scintigrams, anatomically adjusted regions of interest were drawn over infected/inflamed (target) and noninfected/noninflamed (nontarget) thigh, and accumulation of (99m)Tc-UBI (29-41) at sites of infection/inflammation was expressed as a target-to-nontarget (T/NT) ratio. RESULTS: A biodistribution study of (99m)Tc-UBI (29-41) revealed rapid removal of tracer from the circulation via the kidneys (10.6% +/- 2.1% at 5 min and 5.9% +/- 0.8% at 60 min) with accumulation of the major part in the urinary bladder within the first hour after injection (66.6% +/- 7.2%). A significantly higher (P < 0.05) accumulation of (99m)Tc-UBI (29-41) was seen at sites of S. aureus-infected animals (T/NT ratio, 2.2 +/- 0.5) compared with that of E. coli-infected animals (T/NT ratio, 1.7 +/- 0.4). The maximum tracer accumulation was observed at 60 min after injection followed by a gradual decline. No significant accumulation was noticed in thighs of rabbits injected with either turpentine oil or killed S. aureus with markedly lower T/NT ratios (P < 0.05) compared with that of S. aureus- and E. coli-infected thighs. CONCLUSION: A (99m)Tc-UBI (29-41) freeze-dried kit can be used for differentiating infections with S. aureus and E. coli with significantly higher scintigraphic intensity (P < 0.05) compared with that of sterile inflammatory sites. The optimum time for infection imaging is 60 min after injection. Relatively low (T/NT) ratios were observed in E. coli infections compared with those of the S. aureus group, which may be due to a low virulence of the former; however, other possible reasons may include low affinity of this peptide for E. coli microbial membranes.