Behr T M, Becker W S, Klein M W, Bair H J, Scheele J R, Wolf F G
Department of Nuclear Medicine, Friedrich-Alexander-University Erlangen-Nuremberg, Germany.
Cancer Res. 1995 Dec 1;55(23 Suppl):5786s-5793s.
The goal of this study was to intraindividually compare a complete versus a fragmented, directly 99mTc-labeled, monoclonal anti-carcinoembryonic antigen (CEA) antibody, with respect to their antigen-targeting kinetics, sensitivity, and diagnostic accuracy in patients with CEA-expressing tumors. Twenty-five patients were investigated with the 99mTc-labeled anti-CEA IgG1 BW 431/26 and the F(ab')2/Fab' fragment mixture F023C5 within 7 days. For quantitative analysis, the region of interest technique was applied to planar scans, whole-body scans, and single photon emission computed tomography slices 10 min to 48 h postinjection (PI). Final correlations were performed according to the histopathology after surgery or biopsy. Earliest tumor detection was possible with complete IgG1 4 h PI (52% of finally positive lesions). Twenty-four- or even 48-h scans were necessary in 48% of finally positive lesions; tumor detection with fragments was possible in 17% at 1 h PI and in 94% at 4 h PI. With both monoclonal antibodies, in 35%, single photon emission computed tomography was necessary for tumor detection. Absolute antibody uptake in tumor lesions was higher with complete monoclonal antibodies than with fragments. The sensitivity of fragments was higher in detecting primary tumors, local recurrences, and lymph node metastases. For detection of liver metastases, sensitivity was also higher for fragments than for IgG (87 versus 73%), but in scintigraphically positive lesions, tumor:background ratios were significantly lower with fragments (1.26 +/- 0.12 versus 1.70 +/- 0.32; P < 0.01). Therefore, fragments seem to be more suitable for earlier detection of lesions known for their good vascularization, vascular permeability, and antigen accessibility, such as local recurrences, lymph node metastases, and peritoneal carcinomatoses. In liver metastases (high interstitial pressure, low vascular leakage), sensitivity of fragments is higher, but their rapid serum and whole-body clearance lead to a lower absolute antibody uptake, with the consequence of significantly lower tumor:background ratios than with IgG.
本研究的目的是在个体内比较完整的与片段化的、直接用99mTc标记的单克隆抗癌胚抗原（CEA）抗体，比较它们在表达CEA肿瘤患者中的抗原靶向动力学、敏感性和诊断准确性。25例患者在7天内接受了99mTc标记的抗CEA IgG1 BW 431/26和F(ab')2/Fab'片段混合物F023C5的检查。为进行定量分析，在注射后10分钟至48小时对平面扫描、全身扫描和单光子发射计算机断层扫描切片应用感兴趣区技术。最终相关性根据手术或活检后的组织病理学进行。注射后4小时，完整的IgG1可最早检测到肿瘤（最终呈阳性病变的52%）。48%最终呈阳性的病变需要24小时甚至48小时扫描；注射后1小时，17%的病变可用片段检测到肿瘤，4小时时为94%。使用两种单克隆抗体时，35%的病例需要单光子发射计算机断层扫描来检测肿瘤。肿瘤病变中完整单克隆抗体的绝对抗体摄取高于片段。片段在检测原发性肿瘤、局部复发和淋巴结转移方面的敏感性更高。对于肝转移的检测，片段的敏感性也高于IgG（87%对73%），但在闪烁显像呈阳性的病变中，片段的肿瘤与背景比值显著更低（1.26±0.12对1.70±0.32；P<0.01）。因此，片段似乎更适合于早期检测那些以血管化良好、血管通透性高和抗原可及性好为特点的病变，如局部复发、淋巴结转移和腹膜癌转移。在肝转移（间质压力高、血管渗漏低）中，片段的敏感性更高，但它们在血清和全身的快速清除导致绝对抗体摄取较低，结果是肿瘤与背景比值显著低于IgG。
