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抗菌肽99mTc-泛素杀菌肽29-41作为人类感染显像剂:临床试验

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

作者信息

Akhtar Muhammad Saeed, Qaisar Aitzaz, Irfanullah Javaid, Iqbal Javaid, Khan Bashar, Jehangir Mustansar, Nadeem Muhammad Afzal, Khan Muhammad Aleem, Afzal Muhammad Shahzad, Ul-Haq Ikram, Imran Muhammad Babar

机构信息

Punjab Institute of Nuclear Medicine, Faisalabad, Pakistan.

出版信息

J Nucl Med. 2005 Apr;46(4):567-73.

PMID:15809477
Abstract

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.

摘要

未标注

泛癸利定(UBI)29 - 41是一种阳离子合成抗菌肽片段,它优先在感染部位与阴离子微生物细胞膜结合。本研究旨在评估其作为人体感染显像剂的潜力。

方法

本研究纳入了18例疑似骨、软组织或假体感染的患者,其中9例女性,9例男性(平均年龄31.7岁;范围5 - 75岁)。成人静脉注射剂量为400μg/370 - 400MBq的(99m)Tc - UBI 29 - 41。在30、60、120和240分钟进行动态研究,随后对疑似感染区域(靶区)和相应正常区域(非靶区)进行定点观察。用靶区与非靶区比值来确定最佳显像时间。在30、120和240分钟还采集了全身前后位图像以研究生物分布。每个器官的活性以保留剂量的百分比表示。视觉评分(0 - 3分)用于将研究分类为阳性或阴性,0分(摄取极少或无摄取;等同于软组织)和1分(轻度;摄取低于肝脏)被视为阴性,2分(中度;摄取大于或等于肝脏)和3分(强烈;摄取大于或等于肾脏)被视为阳性。扫描结果根据以细菌培养为主要标准以及临床检查、放射学检查和三相骨扫描结果为次要标准,判断为真阳性或假阳性、真阴性或假阴性。

结果

生物分布研究显示,肾脏活性占给药剂量的百分比逐渐下降,从30分钟时的6.53%±0.58%降至120分钟时的4.54%±0.57%,240分钟时为3.38%±0.55%。肝脏也呈现类似趋势,30、120和240分钟时的值分别为5.43%±0.76%、3.17%±0.25%和2.02%±0.30%。放射性逐渐在膀胱中蓄积,30分钟时为4.60%±0.92%,120分钟时为23.00%±2.32%,240分钟时为38.85%±4.01%。在18例用(99m)Tc - UBI 29 - 41进行的研究中,14例显示阳性结果,4例显示阴性结果。阴性结果随后被确认为真阴性。1例扫描的阳性结果被判定为假阳性,因为细菌培养未生长,次要标准也未发现感染证据。10例使用主要标准,4例使用次要标准进行解读。定量分析显示,30分钟时平均靶区与非靶区比值最高为2.75±1.69,120分钟时降至2.04±1.01。总体敏感性、特异性和准确性分别为100%、80%和94.4%。在图像采集期间及研究后5天内未观察到不良反应。

结论

(99m)Tc - UBI 29 - 41在定位感染灶方面显示出前景,30分钟时显像最佳。

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