Yoshida K, Fujikawa T, Tanabe A, Sakurai K
Department of Surgery, Jikei University School of Medicine.
Nihon Shokakibyo Gakkai Zasshi. 1992 Aug;89(8):1506-11.
Route of administration is an important determinant in tumor uptake of monoclonal antibody (mAb). We studied the extraction efficacy of intraportal injection (IP) on tumor uptake over time in hepatic metastases of human colon carcinoma (HT-29LMM) in nude mice. H-15, a murine IgG1 mAb reactive with HT-29LMM was labeled with I-125, and injected at dose of 0.1 microgram and 1.0 microgram intraportally (IP) or intravenously (IV). More than 3 animals per group were sacrificed immediately, 1 h, 24 h, 72 h, and 120 h following injection. Hepatic metastases, normal liver tissue, and blood were weighted and counted for radioactivity. Compared to IV, IP injection resulted in higher (P less than 0.01) percent injection dose per gram (%ID/g) in metastases at all time points for both doses. Metastases: blood and metastases: liver uptake ratios were higher (P less than 0.05) on day 3 and 5 for both IP doses compared to IV doses. Significant improvement in tumor uptake was seen following IP injection of specific mAb; this has important implications on the design of clinical trials using mAb.
给药途径是单克隆抗体(mAb)肿瘤摄取的一个重要决定因素。我们研究了门静脉注射(IP)对裸鼠人结肠癌(HT - 29LMM)肝转移瘤随时间的肿瘤摄取的提取效果。与HT - 29LMM反应的鼠IgG1单克隆抗体H - 15用I - 125标记,并以0.1微克和1.0微克的剂量经门静脉(IP)或静脉(IV)注射。每组超过3只动物在注射后立即、1小时、24小时、72小时和120小时处死。对肝转移瘤、正常肝组织和血液进行称重并计数放射性。与静脉注射相比,两种剂量在所有时间点门静脉注射导致转移瘤中每克注射剂量百分比(%ID/g)更高(P < 0.01)。两种门静脉注射剂量的转移瘤:血液和转移瘤:肝脏摄取率在第3天和第5天比静脉注射剂量更高(P < 0.05)。经门静脉注射特异性单克隆抗体后肿瘤摄取有显著改善;这对使用单克隆抗体的临床试验设计具有重要意义。