Aligning physics and physiology: Engineering antibodies for radionuclide delivery.
Aligning physics and physiology: Engineering antibodies for radionuclide delivery.
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DOI：
10.1002/jlcr.3622
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发表时间：
2018-07
影响因子：
1.8
通讯作者：
Wu AM
中科院分区：
文献类型：
--
作者：
Tsai WK;Wu AM
抗体和抗体片段的精致特异性使其成为靶向递送放射性核素的优秀试剂。放射性标记的抗体和片段已成功地用于肿瘤学和免疫学中细胞表面靶标的分子成像和放射免疫治疗（RIT）。蛋白质工程已被用于临床应用所必需的抗体人源化，以及优化重要特征，包括药代动力学，生物分布和清除。尽管完整抗体作为成像剂和治疗剂具有很高的潜力，但挑战包括血液中的循环时间长，这导致注射后成像时间点较晚和血液吸收剂量较高，这可能对RIT不利。利用工程化片段可以解决这些挑战，因为尺寸减小和Fc功能的去除降低了血清半衰期。放射性标记片段和预靶向策略可在数小时至数天内产生高对比度图像，并降低正常组织中的RIT毒性。此外，片段可以被工程化以指导肝或肾清除，这可以基于应用和疾病环境来选择。本文综述了放射性核素（正电子，γ，β，α和俄歇发射体）与抗体和片段的物理特性，并强调了工程抗体和片段在临床前和临床开发成像和治疗的最新进展。
The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell-surface targets in oncology and immunology. Protein engineering has been employed for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance. Although intact antibodies have high potential as imaging and therapeutic agents, challenges include long circulation time in blood, which leads to later imaging time points post-injection and higher blood absorbed dose that may be disadvantageous for RIT. Utilizing engineered fragments may address these challenges, as size reduction and removal of Fc function decreases serum half-life. Radiolabeled fragments and pretargeting strategies can result in high contrast images within hours to days, and a reduction of RIT toxicity in normal tissues. Additionally, fragments can be engineered to direct hepatic or renal clearance, which may be chosen based on the application and disease setting. This review discusses aligning the physical properties of radionuclides (positron, gamma, beta, alpha, and Auger-emitters) with antibodies and fragments, and highlights recent advances of engineered antibodies and fragments in preclinical and clinical development for imaging and therapy.
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影响因子：
3.1
作者：
Adumeau P;Sharma SK;Brent C;Zeglis BM
通讯作者：
Zeglis BM
影响因子：
3.6
作者：
Freise AC;Wu AM
通讯作者：
Wu AM
DOI：
10.1007/s00259-013-2658-6
发表时间：
2014-05-01
影响因子：
9.1
作者：
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通讯作者：
Lastoria, Secondo
DOI：
10.1007/s002590000272
发表时间：
2000-07-01
期刊：
EUROPEAN JOURNAL OF NUCLEAR MEDICINE
影响因子：
--
作者：
Behr, TM;Béhé, M;Becker, W
通讯作者：
Becker, W
影响因子：
12.8
作者：
Frejd FY;Kim KT
通讯作者：
Kim KT