用中性粒细胞特异性的锝-99m标记单克隆抗体抗SSEA-1对炎症性疾病进行成像。

Imaging inflammatory diseases with neutrophil-specific technetium-99m-labeled monoclonal antibody anti-SSEA-1.

作者信息

Thakur M L, Marcus C S, Henneman P, Butler J, Sinow R, Diggles L, Minami C, Mason G, Klein S, Rhodes B

机构信息

Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

J Nucl Med. 1996 Nov;37(11):1789-95.

PMID:8917176

Abstract

UNLABELLED

Imaging inflammatory diseases with a 99mTc-labeled neutrophil-specific agent that can be injected directly intravenously continues to be a challenge.

METHODS

The antibody, anti-SSEA-1, chosen from studies of 10 neutrophil-specific MAbs, recognizes CD-15 antigens (5.1 x 10(5)/human PMN) with a high association constant (kd = 10(-11) M). One hundred micrograms of MAb labeled with 10-20 mCi 99mTc either by a direct or DTPA conjugation method were injected intravenously into 12 patients (9 men, 3 women, aged 19-48 yr) with clinical evidence of ongoing inflammatory processes. Vital signs of all patients were recorded before and up to 3 hr following administration of the MAb. HAMA was determined in two patients. Anterior and posterior spot views and whole-body images were obtained. All patients except one underwent biopsy, US or CT examinations and/or surgical procedures. Blood samples collected from five patients were analyzed. In nine patients, quantitative organ distribution was determined and radiation dosimetry was calculated.

RESULTS

Labeling yields were 94.8% +/- 1.4% and 95.8% +/- 3.5%, respectively. All patients had unequivocally positive images within 3 hr of the MAb injection. Eleven of these were confirmed by other modalities. One patient recovered on antibiotics and was sent home without surgery or other procedures. The lack of radioactivity in the thyroid or gastrointestinal tract indicated that the in vivo stability of the agent was excellent. At 3 hr postinjection, bladder activity in six patients was 1.3% +/- 0.4% of the administered dose. At this time, splenic uptake (7.7% +/- 1.0% ad. dose) and red marrow uptake (14 +/- 1.8%) were lower than those of 111In-WBC. At 49.0% +/- 3.2% administrated dose, liver uptake was at the upper limit with 111In-WBC uptake. Renal uptake was only 2.4% +/- 0.03% administered dose. At 2 hr postinjection, 14% to 51% of the radioactivity was associated with PMN. Radioactivity with lymphocytes was 0.7% to 10.9%, 1.2% to 4.3% with platelets and 1.1% to 2.4% with RBC. No HAMA were detectable in either patient, and no adverse reaction was detectable in any patient.

CONCLUSION

Results are highly encouaging and have prompted us to prepare a kit for instant preparation and to initiate clinical trials.

摘要

未标记

使用可直接静脉注射的99mTc标记的中性粒细胞特异性试剂对炎症性疾病进行成像仍然是一项挑战。

方法

从10种中性粒细胞特异性单克隆抗体的研究中选择的抗SSEA-1抗体，以高结合常数（kd = 10(-11) M）识别CD-15抗原（5.1 x 10(5)/人中性粒细胞）。采用直接法或DTPA偶联法将100μg用10 - 20mCi 99mTc标记的单克隆抗体静脉注射入12例（9例男性，3例女性，年龄19 - 48岁）有持续炎症过程临床证据的患者体内。在给予单克隆抗体之前及之后3小时内记录所有患者的生命体征。对两名患者进行了人抗鼠抗体（HAMA）检测。获取前后位局部视图和全身图像。除一名患者外，所有患者均接受了活检、超声或CT检查和/或外科手术。对从五名患者采集的血样进行了分析。对九名患者测定了定量器官分布并计算了辐射剂量学。

结果

标记率分别为94.8%±1.4%和95.8%±3.5%。所有患者在注射单克隆抗体后3小时内图像均明确为阳性。其中11例经其他检查方法证实。一名患者使用抗生素后康复，未进行手术或其他操作即被送回家。甲状腺或胃肠道无放射性表明该试剂的体内稳定性极佳。注射后3小时，六名患者膀胱内的放射性活度为给药剂量的1.3%±0.4%。此时，脾脏摄取（给药剂量的7.7%±1.0%）和红骨髓摄取（14±1.8%）低于111In - 白细胞。肝脏摄取为给药剂量的49.0%±3.2%，处于111In - 白细胞摄取的上限。肾脏摄取仅为给药剂量的2.4%±0.03%。注射后2小时，14%至51%的放射性与中性粒细胞相关。与淋巴细胞相关的放射性为0.7%至10.9%，与血小板相关的为1.2%至4.3%，与红细胞相关的为1.1%至2.4%。两名患者均未检测到HAMA，且任何患者均未检测到不良反应。