Storto G, Buchegger F, Waibel R, Kuenzi G, Offord R E, Schubiger P A, Gillet M, Delaloye A B
Department of Nuclear Medicine, University Hospital Lausanne, Switzerland.
Cancer Biother Radiopharm. 2001 Oct;16(5):371-9. doi: 10.1089/108497801753354276.
An 131I labeled trivalent antigen binding construct, formed from 3 Fab' fragments of murine anti-CEA monoclonal antibody (Mab) 35, has shown favorable biokinetics in animal studies.
The aim of this study was to evaluate biodistribution and tumor uptake of 131I-F(ab')3 in patients and its potential utility for radioimmunotherapy of CEA expressing tumors.
Six patients (5 M, 1 F; age 62 +/- 13 y) with liver metastases of colorectal cancer, scheduled for hepatic surgery were studied by 2-3 whole body scans immediately post infusion of 111-137 MBq of 131I labeled Mab 35 F(ab')3 and up to 72 h. Circulating CEA ranged from 1.2 to 1930 ng/ml. We evaluated plasma and whole body clearance, activity accumulation by post-surgical ex-vivo tissue measurement in primary tumor (T) and metastases (M), and calculated M to blood (M/B) and M to liver (M/L) ratios.
All known tumor sites were detected by immunoscintigraphy and confirmed at surgery. Whole body effective T1/2 calculated in two patients was 51.5 h and 55.6 h respectively. Effective serum T1/2 was mono-exponential in 3 patients (short observation interval) with 20.9 +/- 7 h and bi-exponential in three with alpha T1/2 of 6.3 +/- 1 h and beta T1/2 of 38.6 +/- 5 h. In a patient with concomitant colic and hepatic lesions uptake of primary tumor was 0.0071% injected dose per gram of tissue (%ID/g) and mean metastases activity was 0.0275 %ID/g at 48 h. In the 3 patients who had surgery at 48 h, mean uptake in metastases and normal liver was 0.0182 %ID/g and 0.0021 %ID/g, respectively (M/L 8.67). In the single subject followed until 7 days post infusion, residual activity in liver metastases was 10 times higher than in normal parenchyma.
Tumor uptake and tumor to blood ratio, as well as serum clearance of the triconstruct are similar to those observed with intact iodinated anti-CEA antibodies. In the patient studied for 7 days the tumor residence time was favorable. Further improvements, however, need to be obtained before considering this approach for radioimmunotherapy.
由鼠抗癌胚抗原单克隆抗体（Mab）35的3个Fab'片段形成的131I标记的三价抗原结合构建体在动物研究中显示出良好的生物动力学特性。
本研究旨在评估131I-F(ab')3在患者体内的生物分布和肿瘤摄取情况及其对表达癌胚抗原肿瘤进行放射免疫治疗的潜在效用。
6例（5例男性，1例女性；年龄62±13岁）计划进行肝脏手术的结直肠癌肝转移患者，在静脉注射111 - 137 MBq的131I标记的Mab 35 F(ab')3后立即进行2 - 3次全身扫描，观察时间长达72小时。循环癌胚抗原范围为1.2至137 ng/ml。我们评估了血浆和全身清除率、通过手术切除后的离体组织测量计算原发性肿瘤（T）和转移灶（M）中的活性积聚，并计算了M与血液（M/B）以及M与肝脏（M/L）的比值。
所有已知肿瘤部位均通过免疫闪烁显像检测到并在手术中得到证实。两名患者计算出的全身有效半衰期分别为51.5小时和55.6小时。3例患者（观察间隔短）的有效血清半衰期呈单指数形式，为20.9±7小时，3例呈双指数形式，α半衰期为6.3±1小时，β半衰期为38.6±5小时。在一名伴有结肠和肝脏病变的患者中，原发性肿瘤在48小时时的摄取量为每克组织0.0071%注射剂量（%ID/g），转移灶的平均活性为0.0275 %ID/g。在48小时进行手术的3例患者中，转移灶和正常肝脏的平均摄取量分别为0.0182 %ID/g和0.0021 %ID/g（M/L为8.67）。在随访至输注后7天的单一受试者中，肝转移灶中的残留活性比正常实质高10倍。
三构建体的肿瘤摄取和肿瘤与血液比值以及血清清除率与完整碘化抗癌胚抗原抗体观察到的情况相似。在研究7天的患者中，肿瘤停留时间良好。然而，在考虑将此方法用于放射免疫治疗之前，还需要进一步改进。
