Authors' Affiliations: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Cancer Immunol Res. 2013 Aug;1(2):134-43. doi: 10.1158/2326-6066.CIR-13-0007. Epub 2013 May 20.
Radioimmunotherapy (RIT) with (131)I-labeled L19SIP (radretumab; a small immunoprotein format antibody directed against the ED-B domain of fibronectin; ∼ 80 kDa molecular weight) has been investigated in several clinical trials. Here, we describe the use of immuno-PET imaging with iodine-124 ((124)I)-labeled L19SIP to predict doses delivered to tumor lesions and healthy organs by a subsequent radretumab RIT in patients with brain metastases from solid cancer. Bone marrow doses were evaluated both during the diagnostic phase and posttherapy, measuring activities in blood (germanium detector) and whole body (lanthanum bromide detector). Expected doses for radretumab administration (4,107 MBq/m(2)) were calculated from data obtained after administration of an average of 167 MBq (124)I-L19SIP to 6 patients. To assess lesion average doses, the positron emission tomography (PET) scanner was calibrated for the use of (124)I with an International Electrotechnical Commission (IEC) Body Phantom and recovery coefficients were calculated. The average dose to bone red marrow was 0.21 Gy/GBq, with high correlation between provisional and actual posttherapy doses. Although the fraction of injected activity in normal organs was similar in different patients, the antibody uptake in the neoplastic lesions varied by as much as a factor of 60. Immuno-PET with (124)I-labeled L19SIP offers significant advantages over conventional (131)I imaging, in particular accuracy of dosimetric results. Furthermore, the study indicates that antibody uptake can be highly variable even in different lesions of the same patient and that immuno-PET procedures may guide product development with armed antibodies.
放射性免疫疗法 (RIT) 用 (131)I 标记的 L19SIP（radretumab；一种针对纤连蛋白 ED-B 结构域的小分子免疫蛋白格式抗体；分子量约 80 kDa）已在几项临床试验中进行了研究。在这里，我们描述了使用碘-124 ((124)I)-标记的 L19SIP 进行免疫 PET 成像，以预测随后的 radretumab RIT 对来自实体瘤脑转移患者的肿瘤病灶和健康器官的剂量。在诊断阶段和治疗后都评估了骨髓剂量，通过血液（锗探测器）和全身（溴化镧探测器）测量放射性。预期的 radretumab 给药剂量（4,107 MBq/m(2)) 是根据 6 名患者平均给予 167 MBq ((124)I-L19SIP 后获得的数据计算得出的。为了评估病灶平均剂量，使用国际电工委员会 (IEC) 体模对 PET 扫描仪进行了 (124)I 使用校准，并计算了恢复系数。红骨髓的平均剂量为 0.21 Gy/GBq，临时和实际治疗后剂量之间具有高度相关性。尽管不同患者正常器官中注射活性的分数相似，但抗体在肿瘤病变中的摄取差异高达 60 倍。与传统的 (131)I 成像相比，(124)I 标记的 L19SIP 免疫 PET 具有显著优势，特别是剂量学结果的准确性。此外，该研究表明，即使在同一患者的不同病变中，抗体摄取也可能高度变化，并且免疫 PET 程序可能会指导带有武装抗体的产品开发。
