Boerman O C, van Eerd J, Oyen W J, Corstens F H
Department of Nuclear Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands.
J Nucl Med. 2001 Sep;42(9):1405-11.
A new 3-step approach to imaging infectious and inflammatory foci was developed and optimized in a rat model. The approach relies on the nonspecific localization of an anti-diethylenetriaminepentaacetic acid (DTPA) antibody in inflamed tissue. In this study, the 3-step strategy was optimized by selecting the most suitable radiolabeled hapten and tuning the dosing schedule.
Wistar rats with Staphylococcus aureus infection in the left calf muscle were primed with the anti-DTPA antibody DTIn-1 (0.67, 2, or 6 nmol per rat). In the second step (1-24 h later), the anti-DTPA activity in the circulation was blocked with unlabeled bovine serum albumin DTPA-In (0.3, 1, or 3 nmol per rat). In the third step (5-30 min later), the radiolabeled hapten (monovalent or bivalent 111In-DTPA) was administered. The in vivo distribution of the radiolabel was monitored by scintigraphic imaging and by ex vivo counting of dissected tissues.
Scatchard analysis revealed that the affinity of DTIn-1 for bivalent DTPA-111In (111In-diDTPA) was 6 times higher than the affinity for monovalent 111In-DTPA (K(a) = 0.87 x 10(-9) mol/L vs. 5.3 x 10(-9) mol/L). The uptake of the bivalent chelate in the abscess was 2.5-fold higher than that of monovalent 111In-DTPA. Most important, the bivalent chelate was completely retained in the abscess over time. Using the bivalent chelate, the optimal dosing scheme was determined with respect to the DTIn-1 dose (2 nmol per rat), the blocking agent dose (1 nmol per rat), and radiolabeled chelate dose (40 pmol per rat). The procedure was rapid; the infectious focus was clearly visualized 1 h after injection of the 111In-labeled diDTPA, which was 5 h after administration of the anti-DTPA antibody. The nontargeted radiolabel rapidly cleared to the urine, only being retained in the abscess and the kidneys (4-6 percentage injected dose). Finally, an N2S2 core was attached to the diDTPA compound, allowing the use of 99mTc.
This 3-step approach enables rapid imaging of infectious foci with minimal uptake in noninflamed tissues.
在大鼠模型中开发并优化了一种用于成像感染性和炎症病灶的新的三步法。该方法依赖于抗二乙烯三胺五乙酸（DTPA）抗体在炎症组织中的非特异性定位。在本研究中，通过选择最合适的放射性标记半抗原并调整给药方案对三步策略进行了优化。
对左小腿肌肉感染金黄色葡萄球菌的Wistar大鼠用抗DTPA抗体DTIn-1（每只大鼠0.67、2或6 nmol）进行预处理。在第二步（1 - 24小时后），用未标记的牛血清白蛋白DTPA-In（每只大鼠0.3、1或3 nmol）阻断循环中的抗DTPA活性。在第三步（5 - 30分钟后），给予放射性标记的半抗原（单价或双价111In-DTPA）。通过闪烁成像和对解剖组织的离体计数监测放射性标记的体内分布。
Scatchard分析显示，DTIn-1对双价DTPA-111In（111In-二DTPA）的亲和力比对单价111In-DTPA的亲和力高6倍（K(a)=0.87×10(-9)mol/L对5.3×10(-9)mol/L）。脓肿中双价螯合物的摄取比单价111In-DTPA高2.5倍。最重要的是，随着时间的推移，双价螯合物完全保留在脓肿中。使用双价螯合物，确定了关于DTIn-1剂量（每只大鼠2 nmol）、阻断剂剂量（每只大鼠1 nmol）和放射性标记螯合物剂量（每只大鼠40 pmol）的最佳给药方案。该过程迅速；在注射111In标记的二DTPA后1小时，即给予抗DTPA抗体后5小时，感染灶清晰可见。非靶向放射性标记迅速清除到尿液中，仅保留在脓肿和肾脏中（注射剂量的4 - 6%）。最后，将N2S2核心连接到二DTPA化合物上，允许使用99mTc。
这种三步法能够快速成像感染灶，且在非炎症组织中的摄取最小。
