Enhanced Tumor Targeting of Radiolabeled Mouse/Human Chimeric Anti-Tn Antibody in Losartan-Treated Mice Bearing Tn-Expressing Lung Tumors.

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cancer Biotherapy and Radiopharmaceuticals Pub Date : 2024-06-01 Epub Date: 2024-01-12 DOI:10.1089/cbr.2023.0138
Marcos Tassano, Ximena Camacho, Teresa Freire, Carolina Perroni, Valeria da Costa, Mirel Cabrera, Maria Fernanda García, Marcelo Fernandez, Juan Pablo Gambini, Pablo Cabral, Eduardo Osinaga
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Abstract

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.

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放射性标记的小鼠/人嵌合抗 Tn 抗体在洛沙坦治疗的携带 Tn 表达肺肿瘤的小鼠中增强了肿瘤靶向性
目的:用碘-131(131I)和锝-99m(99mTc)对小鼠/人嵌合抗Tn单克隆抗体ChiTn进行放射性标记,以评估其在Tn表达(Tn+)和野生型(Tn-)LL/2肺癌细胞中的生物分布和内化情况。结果:在Tn+细胞中观察到ChiTn的选择性蓄积和逐渐内化。在患有 Tn+ 或 Tn- 肺肿瘤的小鼠体内进行的生物分布表明,肿瘤内放射性标记 ChiTn 的吸收随着时间的推移而增加。99mTc 和 131I 双标记实验显示了不同的生物分布模式,99mTc 在肝、脾和肾中的吸收值较高,而 131I 在甲状腺和胃中的吸收值较高。然而,Tn+和Tn-肿瘤的摄取量并无明显差异。为了提高肿瘤靶向性,研究人员研究了洛沙坦这种已知能增强肿瘤灌注和药物输送的抗高血压药物。对洛沙坦处理的小鼠进行的生物分布研究显示,Tn+肿瘤对放射性标记的ChiTn的摄取量明显更高。对照分子 IgG-HYNIC-99mTc 的摄取量没有明显变化。结论这些研究结果表明,放射性标记的ChiTn在洛沙坦治疗的Tn表达肺肿瘤小鼠中具有更强的肿瘤靶向性。这些研究结果突出了ChiTn作为治疗肿瘤药物的潜力,并强调了洛沙坦作为辅助治疗手段对改善肿瘤灌注和药物输送的重要性。
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来源期刊
CiteScore
7.80
自引率
2.90%
发文量
87
审稿时长
3 months
期刊介绍: Cancer Biotherapy and Radiopharmaceuticals is the established peer-reviewed journal, with over 25 years of cutting-edge content on innovative therapeutic investigations to ultimately improve cancer management. It is the only journal with the specific focus of cancer biotherapy and is inclusive of monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapies. The Journal includes extensive reporting on advancements in radioimmunotherapy, and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments.
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