Ward B G, Mather S J, Hawkins L R, Crowther M E, Shepherd J H, Granowska M, Britton K E, Slevin M L
Cancer Res. 1987 Sep 1;47(17):4719-23.
The localization of i.p. injected, radioiodine conjugated monoclonal antibody HMFG2 was studied in 18 patients with ovarian carcinoma. Patients were injected i.p. at time points up to 168 h before laparotomy, at which time tumor, ascites, normal tissue, and blood samples were removed and the contained radioactivity measured. In the first 10 patients, localization was compared with that of a simultaneously injected irrelevant (nonspecific) antibody (UJ13A) of the same immunoglobulin class and, in the subsequent 8 patients, with HMFG2 administered i.v. After i.p. injection, HMFG2-radioiodine was found in concentrations of 0.0001-0.0030% of the injected amount per gram in solid tumor, 0.0363-0.02560%/g in ascites, 0.0003-0.0017%/g in blood, and 0.001-0.0012%/g in normal tissue. Tumor:normal tissue ratios of 0.9-10.0 and tumor:blood ratios of 0.3-4.0 were seen up to 168 h after injection. Localization of the HMFG2 conjugate was consistently greater than that of the irrelevant antibody. For solid tumor, the i.v. route of administration resulted in consistently higher absolute levels of HMFG2 conjugate uptake but tumor:blood and tumor:normal tissue ratios were similar. On the other hand the i.p. route of administration offered consistent advantages of 4- to 71-fold over the i.v. route when HMFG2 conjugate localization on ascites cells was examined. Ascites:normal tissue and ascites:blood ratios of up to 512 and 448, respectively, were achieved. After i.p. injection, radioiodine was cleared from the body exponentially with a half-life of 50 h. Maximum circulating blood levels of 8.6 +/- 2.0% injected activity were seen at 48 h and these then decreased with a t 1/2 value of 38 h. Over 80% of injected activity was cleared in the urine as nonprotein bound iodine by 168 h.
对18例卵巢癌患者进行研究,观察腹腔注射放射性碘标记单克隆抗体HMFG2后的定位情况。在剖腹手术前长达168小时的不同时间点对患者进行腹腔注射,然后在剖腹手术时采集肿瘤、腹水、正常组织和血液样本,并测量其中所含的放射性。在最初的10例患者中,将HMFG2的定位情况与同时注射的相同免疫球蛋白类别的无关(非特异性)抗体(UJ13A)进行比较;在随后的8例患者中,将其与静脉注射的HMFG2进行比较。腹腔注射后,在实体瘤中发现HMFG2 - 放射性碘的浓度为每克注射量的0.0001 - 0.0030%,腹水中为0.0363 - 0.02560%/克,血液中为0.0003 - 0.0017%/克,正常组织中为0.001 - 0.0012%/克。注射后长达168小时,肿瘤与正常组织的比值为0.9 - 10.0,肿瘤与血液的比值为0.3 - 4.0。HMFG2偶联物的定位始终高于无关抗体。对于实体瘤,静脉注射途径导致HMFG2偶联物摄取的绝对水平始终较高,但肿瘤与血液以及肿瘤与正常组织的比值相似。另一方面,当检查HMFG2偶联物在腹水细胞上的定位时,腹腔注射途径相对于静脉注射途径具有4至71倍的持续优势。腹水与正常组织以及腹水与血液的比值分别高达512和448。腹腔注射后,放射性碘以指数形式从体内清除,半衰期为50小时。在48小时时观察到循环血液中放射性活度的最高水平为注射活度的8.6±2.0%,随后以38小时的t 1/2值下降。到168小时时,超过80%的注射活度以非蛋白结合碘的形式经尿液清除。