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癌症研究中的放射免疫诊断

Radioimmunotheragnosis in Cancer Research.

作者信息

Garaulet Guillermo, Báez Bárbara Beatriz, Medrano Guillermo, Rivas-Sánchez María, Sánchez-Alonso David, Martinez-Torrecuadrada Jorge L, Mulero Francisca

机构信息

Molecular Imaging Unit, Spanish National Cancer Center-CNIO, 28029 Madrid, Spain.

Protein Production Unit, Spanish National Cancer Center-CNIO, 28029 Madrid, Spain.

出版信息

Cancers (Basel). 2024 Aug 20;16(16):2896. doi: 10.3390/cancers16162896.

Abstract

The combination of immunoPET-where an antibody (Ab) is labeled with an isotope for PET imaging-and radioimmunotherapy (RIT), using the same antibody with a therapeutic isotope, offers significant advantages in cancer management. ImmunoPET allows non-invasive imaging of antigen expression, which aids in patient selection for subsequent radioimmunotherapy. It also facilitates the assessment of tumor response to therapy, allowing for treatment adjustments if necessary. In addition, immunoPET provides critical pharmacokinetic data, including antibody biodistribution and clearance rates, which are essential for dosimetry calculations and treatment protocol optimization. There are still challenges to overcome. Identifying appropriate target antigens that are selectively expressed on cancer cells while minimally expressed on normal tissues remains a major hurdle to reduce off-target toxicity. In addition, it is critical to optimize the pharmacokinetics of radiolabeled antibodies to maximize tumor uptake and minimize normal tissue uptake, particularly in vital organs such as the liver and kidney. This approach offers the potential for targeted and personalized cancer therapy with reduced systemic toxicity by exploiting the specificity of monoclonal antibodies and the cytotoxic effects of radiation. However, further research is needed to address remaining challenges and to optimize these technologies for clinical use.

摘要

免疫正电子发射断层扫描(immunoPET)(将抗体(Ab)用同位素标记用于正电子发射断层扫描成像)与放射免疫疗法(RIT)相结合,使用带有治疗性同位素的相同抗体,在癌症治疗中具有显著优势。免疫正电子发射断层扫描能够对抗原表达进行无创成像,这有助于为后续的放射免疫疗法选择患者。它还便于评估肿瘤对治疗的反应,必要时可据此调整治疗方案。此外,免疫正电子发射断层扫描提供关键的药代动力学数据,包括抗体的生物分布和清除率,这对于剂量计算和治疗方案优化至关重要。仍有一些挑战需要克服。识别在癌细胞上选择性表达而在正常组织上最少表达的合适靶抗原,仍然是降低脱靶毒性的主要障碍。此外,优化放射性标记抗体的药代动力学以最大化肿瘤摄取并最小化正常组织摄取至关重要,尤其是在肝脏和肾脏等重要器官中。这种方法通过利用单克隆抗体的特异性和辐射的细胞毒性作用,具有实现靶向和个性化癌症治疗并降低全身毒性的潜力。然而,需要进一步研究以应对剩余挑战并优化这些技术以供临床使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/303a/11352548/e95ce89d577f/cancers-16-02896-g001.jpg

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