Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Int J Mol Sci. 2024 Oct 5;25(19):10737. doi: 10.3390/ijms251910737.
Preliminary studies on a radioactive antibody against the neural cell adhesion molecule (NCAM) demonstrated a significant accumulation of [I]I-ERIC1 in neuroblastoma tumor cells in mice. This study aims to validate the therapeutic efficacy and potential adverse effects of these radioactive immunoconjugates (RICs) in neuroblastoma-bearing mice. To determine the highest tolerated dose, healthy SCID mice received 1 to 22 MBq of [I]I-ERIC1, with the survival time measured. Tumor response was evaluated by administering 0.8 to 22 MBq of [I]I-ERIC1 to neuroblastoma-bearing mice and assessing tumor size and systemic toxicity through body weight, blood counts, and survival. It was observed that doses up to approximately 3 MBq per animal (150 MBq/kg) were well tolerated, whereas higher doses resulted in systemic toxicity and death. The neuroblastomas exhibited a dose-dependent response, with optimal therapeutic efficacy achieved at 1.8-2.5 MBq per animal (90-125 MBq/kg), significantly extending survival by a factor of five. The antibody ERIC1 is a promising vehicle for the transport of beta emitters into NCAM-positive tumor tissue. An optimal dosage of the [I]I-ERIC1 antibody can be established with a balance of tumor-static effects and adverse effects, resulting in a marked extension of survival time.
针对神经细胞黏附分子（NCAM）的放射性抗体的初步研究表明，[I]I-ERIC1 在小鼠神经母细胞瘤肿瘤细胞中有明显的聚集。本研究旨在验证这些放射性免疫偶联物（RICs）在荷神经母细胞瘤小鼠中的治疗效果和潜在的不良反应。为了确定最高耐受剂量，健康的 SCID 小鼠接受了 1 到 22MBq 的[I]I-ERIC1，并测量了存活时间。通过给予荷神经母细胞瘤的小鼠 0.8 到 22MBq 的[I]I-ERIC1，评估肿瘤反应，并通过体重、血细胞计数和存活来评估肿瘤大小和全身毒性。结果表明，高达约 3MBq/只动物（150MBq/kg）的剂量可以很好地耐受，而更高的剂量会导致全身毒性和死亡。神经母细胞瘤表现出剂量依赖性反应，在 1.8-2.5MBq/只动物（90-125MBq/kg）的最佳治疗效果下，显著延长了 5 倍的存活时间。抗体 ERIC1 是将β发射器输送到 NCAM 阳性肿瘤组织的有前途的载体。通过肿瘤稳定作用和不良反应之间的平衡，可以确定[I]I-ERIC1 抗体的最佳剂量，从而显著延长存活时间。
