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首页> 外文期刊>Molecular imaging and biology: MIB : the official publication of the Academy of Molecular Imaging >Biodistribution, pharmacokinetics, and nuclear imaging studies of 111in-labeled rGel/BLyS fusion toxin in SCID mice bearing B cell lymphoma
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Biodistribution, pharmacokinetics, and nuclear imaging studies of 111in-labeled rGel/BLyS fusion toxin in SCID mice bearing B cell lymphoma

机译：111in标记的rGel / BLyS融合毒素在携带B细胞淋巴瘤的SCID小鼠中的生物分布，药代动力学和核成像研究

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Purpose: We examined the biodistribution and pharmacokinetics of 111In-labeled rGel/BLyS, a gelonin toxin (rGel)-B lymphocyte stimulator (BLyS) fusion protein. Materials and Methods: rGel/BLyS was labeled with In-111 through DTPA with a labeling efficiency 95%. Biodistribution/imaging studies were obtained in severe-combined immunodeficiency mice bearing diffuse large B cell lymphoma OCI-Ly10. Pharmacokinetic studies were performed in BALB/c mice. Results: In vitro, DTPA-conjugated rGel/BLyS displayed selective cytotoxicity against OCI-Ly10 cells and mantle cell lymphoma JeKo cells. In vivo, rGel/BLyS exhibited a tri-exponential disposition with a rapid initial mean distribution followed by an extensive mean distribution and a long terminal elimination phase. At 48 h after injection, uptake of the radiotracer in tumors was 1.25%ID/g, with a tumor-to-blood ratio of 13. Tumors were clearly visualized at 24-72 h postinjection. Micro-SPECT-CT images and ex vivo analyses confirmed the accumulation of rGel/BLyS in OCI-Ly10 tumors. Conclusions: 111In- DTPA-rGel/BLyS are distributed to B cell tumors and induce apoptosis in tumors. Preclinical antitumor studies using rGel/BLyS should use a twice-per-week treatment schedule.
机译：目的：我们检查了111In标记的rGel / BLyS（一种明胶毒素（rGel）-B淋巴细胞刺激物（BLyS）融合蛋白）的生物分布和药代动力学。材料和方法：rGel / BLyS通过DTPA用In-111标记，标记效率> 95％。生物分布/成像研究在携带弥漫性大B细胞淋巴瘤OCI-Ly10的严重合并免疫缺陷小鼠中获得。在BALB / c小鼠中进行了药代动力学研究。结果：在体外，结合DTPA的rGel / BLyS对OCI-Ly10细胞和套细胞淋巴瘤JeKo细胞表现出选择性的细胞毒性。在体内，rGel / BLyS表现出三指数分布，具有快速的初始均值分布，然后是广泛的均值分布和较长的末端消除阶段。在注射后48小时，肿瘤中放射性示踪剂的摄取为1.25％ID / g，肿瘤与血液的比率为13。在注射后24-72小时清晰可见肿瘤。微型SPECT-CT图像和离体分析证实了rGel / BLyS在OCI-Ly10肿瘤中的蓄积。结论：111In-DTPA-rGel / BLyS分布于B细胞肿瘤并诱导肿瘤细胞凋亡。使用rGel / BLyS进行的临床前抗肿瘤研究应采用每周两次的治疗方案。

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