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.
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.
Authors: Filipa Mota; Alvaro A Ordonez; George Firth; Camilo A Ruiz-Bedoya; Michelle T Ma; Sanjay K Jain Journal: J Med Chem Date: 2020-02-21 Impact factor: 7.446