68Ga Radiolabeling of NODASA-Functionalized Phage Display–Derived Peptides for Prospective Assessment as Tuberculosis-Specific PET Radiotracers

IF 0.9 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-08-08 DOI:10.1002/jlcr.4120
Christiaan A. Gouws, Tricia Naicker, Beatriz G. de la Torre, Fernando Albericio, Janie Duvenhage, Hendrik G. Kruger, Biljana Marjanovic-Painter, Sipho Mdanda, Jan R. Zeevaart, Thomas Ebenhan, Thavendran Govender
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Abstract

This research presents the development of positron emission tomography (PET) radiotracers for detecting Mycobacterium tuberculosis (MTB) for the diagnosis and monitoring of tuberculosis. Two phage display–derived peptides with proven selective binding to MTB were identified for development into PET radiopharmaceuticals: H8 (linear peptide) and PH1 (cyclic peptide). We sought to functionalize H8/PH1 with NODASA, a bifunctional chelator that allows complexation of PET-compatible radiometals such as gallium-68. Herein, we report on the chelator functionalization, optimized radiosynthesis, and assessment of the radiopharmaceutical properties of [68Ga]Ga-NODASA-H8 and [68Ga]Ga-NODASA-PH1. Robust radiolabeling was achieved using the established routine method, indicating consistent production of a radiochemically pure product (RCP ≥ 99.6%). For respective [68Ga]Ga-NODASA-H8 and [68Ga]Ga-NODASA-PH1, relatively high levels of decay-corrected radiochemical yield (91.2% ± 2.3%, 86.7% ± 4.0%) and apparent molar activity (Am, 3.9 ± 0.8 and 34.0 ± 5.3 GBq/μmol) were reliably achieved within 42 min, suitable for imaging purposes. Notably, [68Ga]Ga-NODASA-PH1 remained stable in blood plasma for up to 2 h, while [68Ga]Ga-NODASA-H8 degraded within 30 min. For both 68Ga peptides, minimal whole-blood cell binding and plasma protein binding were observed, indicating a favorable pharmaceutical behavior. [68Ga]Ga-NODASA-PH1 is a promising candidate for further in vitro/in vivo evaluation as a tuberculosis-specific infection imaging agent.

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68Ga 放射性标记 NODASA 功能化噬菌体展示衍生多肽,用于结核病特异性 PET 放射性标记物的前瞻性评估。
这项研究介绍了用于检测结核分枝杆菌(MTB)的正电子发射断层扫描(PET)放射性药物的开发情况,以诊断和监测结核病。研究人员确定了两种噬菌体展示衍生的肽,它们经证实与 MTB 有选择性结合,可开发成 PET 放射性药物:H8(线性肽)和 PH1(环状肽)。我们试图用 NODASA 对 H8/PH1 进行功能化处理,NODASA 是一种双功能螯合剂,可以与镓-68 等 PET 兼容的放射性金属复合。在此,我们报告了螯合剂的功能化、优化的放射合成以及 [68Ga]Ga-NODASA-H8 和 [68Ga]Ga-NODASA-PH1 的放射性药物特性评估。采用既定的常规方法实现了稳健的放射性标记,表明始终生产出放射性化学纯产品(RCP ≥ 99.6%)。对于[68Ga]Ga-NODASA-H8和[68Ga]Ga-NODASA-PH1,在42分钟内分别可靠地达到了较高的衰变校正放射化学收率(91.2% ± 2.3%,86.7% ± 4.0%)和表观摩尔活度(Am,3.9 ± 0.8和34.0 ± 5.3 GBq/μmol),适合成像目的。值得注意的是,[68Ga]Ga-NODASA-PH1在血浆中可保持稳定达2小时,而[68Ga]Ga-NODASA-H8则在30分钟内降解。这两种 68Ga 肽的全血细胞结合率和血浆蛋白结合率都很低,这表明它们具有良好的药物特性。[68Ga]Ga-NODASA-PH1很有希望作为一种结核特异性感染成像剂接受进一步的体外/体内评估。
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来源期刊
CiteScore
3.30
自引率
0.00%
发文量
57
审稿时长
1 months
期刊介绍: The Journal of Labelled Compounds and Radiopharmaceuticals publishes all aspects of research dealing with labeled compound preparation and applications of these compounds. This includes tracer methods used in medical, pharmacological, biological, biochemical and chemical research in vitro and in vivo. The Journal of Labelled Compounds and Radiopharmaceuticals devotes particular attention to biomedical research, diagnostic and therapeutic applications of radiopharmaceuticals, covering all stages of development from basic metabolic research and technological development to preclinical and clinical studies based on physically and chemically well characterized molecular structures, coordination compounds and nano-particles.
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