van Eerd Julliëtte E M, Laverman Peter, Oyen Wim J G, Harris Thomas D, Edwards D Scott, Ellars Charles E, Corstens Frans H M, Boerman Otto C
Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands.
J Nucl Med. 2004 Jan;45(1):89-93.
The use of radiolabeled leukocytes is considered the gold standard for scintigraphic imaging of inflammatory bowel disease. The disadvantages of (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)-leukocytes, however, encourage the search for new imaging agents with at least similar diagnostic accuracy but without the laborious preparation and subsequent risk of contamination. In this study we investigated the imaging characteristics of a new imaging agent that specifically binds to the leukotriene B(4) (LTB(4)) receptors expressed on neutrophils. Imaging characteristics of the (111)In-labeled LTB(4) antagonist (DPC11870) were compared with those of (18)F-FDG and (99m)Tc-HMPAO-granulocytes in a rabbit model of experimental colitis.
Acute colitis was induced in New Zealand White (NZW) rabbits by infusion of trinitrobenzene sulfonic acid in the descending colon. Forty-eight hours after induction of colitis, all animals were injected intravenously with (99m)Tc-granulocytes, (18)F-FDG, or (111)In-DPC11870. The pharmacokinetics and biodistribution were studied by serial scintigraphic imaging and by ex vivo counting of dissected tissues.
All 3 radiopharmaceuticals showed the inflamed colon as early as 1 h after injection. However, compared with (99m)Tc-granulocytes, both (111)In-DPC11870 and (18)F-FDG were superior in revealing the inflamed lesions. The biodistribution data showed that uptake of (111)In-DPC11870 in the inflamed colon was highest (0.72 +/- 0.18 percentage injected dose per gram [%ID/g]), followed by uptake of (99m)Tc-granulocytes (0.40 +/- 0.11 %ID/g) and of (18)F-FDG (0.16 +/- 0.04 %ID/g). Because of low activity concentrations in the noninflamed colon, the radiolabeled LTB(4) antagonist also revealed the highest ratio of affected colon to unaffected colon (11.6 for (111)In-DPC11870, 5.5 for (99m)Tc-granulocytes, and 4.1 for (18)F-FDG).
The radiolabeled LTB(4) antagonist DPC11870 clearly delineated acute colitis lesions in NZW rabbits within 1 h after injection. Because of high uptake in the inflamed lesions and a low activity concentration in the noninflamed colon, images acquired with (111)In-DPC11870 were better than those acquired with (99m)Tc-granulocytes or (18)F-FDG.
放射性标记白细胞的使用被认为是炎症性肠病闪烁成像的金标准。然而，（99m）锝-六甲基丙烯胺肟（HMPAO）-白细胞的缺点促使人们寻找新的成像剂，其诊断准确性至少相似，但无需繁琐的制备过程以及后续的污染风险。在本研究中，我们研究了一种新的成像剂的成像特性，该成像剂能特异性结合中性粒细胞上表达的白三烯B4（LTB4）受体。在实验性结肠炎的兔模型中，将（111）铟标记的LTB4拮抗剂（DPC11870）的成像特性与（18）氟-脱氧葡萄糖（（18）F-FDG）和（99m）Tc-HMPAO-粒细胞的成像特性进行了比较。
通过向新西兰白兔（NZW）的降结肠注入三硝基苯磺酸诱导急性结肠炎。在诱导结肠炎48小时后，所有动物静脉注射（99m）Tc-粒细胞、（18）F-FDG或（111）In-DPC11870。通过连续闪烁成像和对解剖组织进行体外计数研究药代动力学和生物分布。
所有3种放射性药物在注射后1小时内均显示出炎症结肠。然而，与（99m）Tc-粒细胞相比，（111）In-DPC11870和（18）F-FDG在显示炎症病变方面更具优势。生物分布数据显示，（111）In-DPC11870在炎症结肠中的摄取最高（每克注射剂量的0.72±0.18百分比[％ID/g]），其次是（99m）Tc-粒细胞（0.40±0.11％ID/g）和（18）F-FDG（0.16±0.04％ID/g）。由于非炎症结肠中的活性浓度较低，放射性标记的LTB4拮抗剂也显示出受影响结肠与未受影响结肠的最高比率（（111）In-DPC11870为11.6，（99m）Tc-粒细胞为5.5，（18）F-FDG为4.1）。
放射性标记的LTB4拮抗剂DPC11870在注射后1小时内可清晰勾勒出NZW兔的急性结肠炎病变。由于在炎症病变中的高摄取以及在非炎症结肠中的低活性浓度，用（111）In-DPC11870获得的图像优于用（99m）Tc-粒细胞或（18）F-FDG获得的图像。
