Thédrez P, Saccavini J C, Nolibé D, Simoen J P, Guerreau D, Gestin J F, Kremer M, Chatal J F
Unité 211 INSERM, Faculté de Médecine, Nantes, France.
Cancer Res. 1989 Jun 1;49(11):3081-6.
The purpose of this work was to study the biodistribution of 111In-labeled OC 125 monoclonal antibody (MAb) with known affinity for ovarian carcinomas in a nude mouse model grafted i.p. with a human ovarian cancer (NIH:OVCAR-3). Tumor uptake 24 h after i.p. injection was higher with intact 111In-labeled OC 125 MAb (28 +/- 7.44%ID/g) than with 111In-nonspecific immunoglobulin (6.86 +/- 1.35%ID/g). The kinetics of tumor uptake also differed, showing a plateau followed by a drop at Day 7 with 111In-OC 125 MAb and a decrease beginning at 24 h with 111In-nonspecific immunoglobulin. Tumor-to-normal tissue ratios ranged between 29.91 +/- 11.85 and 0.68 +/- 0.15 with 111In-OC 125 MAb and between 4.50 +/- 1.06 and 0.53 +/- 0.04 with 111In-nonspecific immunoglobulin according to the normal tissues and the time points considered. Tumor uptake 2 h after injection was the same for F(ab')2 fragments as for intact MAb, whereas maximum uptake at 24 h (18.76 +/- 4.62%ID/g) was lower and was followed by a decrease at Day 4. Tumor-to-normal tissue ratios were in the same range, except for the tumor to blood ratio which was higher and the tumor to kidney ratio which was lower at 24 and 96 h. Maximum tumor uptake was higher after i.p. (30.77 +/- 4.76%ID/g) than i.v. (14.59 +/- 2.70%ID/g) injection. Instead of attaining the plateau noted after i.p. injection, tumor uptake after i.v. injection remained low at 2 h (2.11 +/- 1.66%ID/g), reaching its peak only after 96 h. 131I-OC 125 injected i.p., which reached maximum tumor uptake at 2 h (13.53 +/- 4.25%ID/g), showed tumor-to-tissue ratios ranging between 15.98 +/- 2.63 and 0.96 +/- 0.86, i.e., not very different from those with 111In. After i.p. injection of a radiolabeled colloid solution, maximum tumor uptake was reached at 96 h (20.22 +/- 5.35%ID/g), but with very high nonspecific uptake in liver (31.06 +/- 6.22%ID/g) and spleen (55.23 +/- 14.11%ID/g). These results indicate high, selective tumor uptake of 111In-OC 125 after i.p. injection and demonstrate the feasibility of i.p. radioimmunotherapy of ovarian carcinomas.
本研究旨在利用人卵巢癌（NIH:OVCAR-3）腹腔移植裸鼠模型，研究对卵巢癌具有已知亲和力的111In标记的OC 125单克隆抗体（MAb）的生物分布。腹腔注射后24小时，完整的111In标记的OC 125 MAb的肿瘤摄取率（28±7.44%ID/g）高于111In非特异性免疫球蛋白（6.86±1.35%ID/g）。肿瘤摄取动力学也有所不同，111In-OC 125 MAb在第7天出现平台期后下降，而111In非特异性免疫球蛋白在24小时后开始下降。根据所考虑的正常组织和时间点，111In-OC 125 MAb的肿瘤与正常组织比值在29.91±11.85至0.68±0.15之间，111In非特异性免疫球蛋白的肿瘤与正常组织比值在4.50±1.06至0.53±0.04之间。注射后2小时，F(ab')2片段的肿瘤摄取与完整MAb相同，而24小时时的最大摄取率（18.76±4.62%ID/g）较低，随后在第4天下降。肿瘤与正常组织比值在相同范围内，但在24小时和96小时时，肿瘤与血液比值较高，肿瘤与肾脏比值较低。腹腔注射后的最大肿瘤摄取率（30.77±4.76%ID/g）高于静脉注射（14.59±2.70%ID/g）。静脉注射后，肿瘤摄取在2小时时仍较低（2.11±1.66%ID/g），直到96小时才达到峰值，而不是像腹腔注射后那样出现平台期。腹腔注射的131I-OC 125在2小时时达到最大肿瘤摄取率（13.53±4.25%ID/g），肿瘤与组织比值在15.98±2.63至0.96±0.86之间，即与111In的比值没有太大差异。腹腔注射放射性标记的胶体溶液后，96小时时达到最大肿瘤摄取率（20.22±5.35%ID/g），但肝脏（31.06±6.22%ID/g）和脾脏（55.23±14.11%ID/g）的非特异性摄取非常高。这些结果表明腹腔注射后111In-OC 125对肿瘤具有高选择性摄取，并证明了卵巢癌腹腔放射免疫治疗的可行性。
