Pursuing theranostics: a multimodal architecture approach.

IF 3.5 Q2 CHEMISTRY, ANALYTICAL Sensors & diagnostics Pub Date : 2024-10-24 DOI:10.1039/d4sd00221k
Aidan A Bender, Connor K Holiski, Mary Embree, Heather M Hennkens, John R Klaehn, Ellie Lundgreen, Andrew G Roberts, Peter R Zalupski, Tara Mastren
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Abstract

Theranostics is a field of nuclear medicine which uses the same targeting vector and chelating system for both a diagnostic and therapeutic radionuclide, allowing for uniformity in imaging and treatment. This growing field requires the development of more flexible chelate systems that permit novel targeting strategies. Toward this end, a multimodal architecture has been realized, making use of a phosphazene-based core and click chemistry to achieve a flexible and customizable scaffold. The six arm phosphazene-based core can scaffold six DTPA chelating motifs or a mixed set of 3 : 3 DTPA : DFO chelates resulting in two multimodal compounds, pDbDt and pDbDtDf, respectively. Terbium complexes displayed strong luminescence, supporting that the structures act as an organic antenna for luminescence. Metal displacement titration studies confirmed the desired structures as well as the capability for heterometallic labeling of the structures. These structures were found to have high thermal and biological stability in vitro. Radiolabeling of each compound resulted in high molar activity labeling of each compound: 169 MBq nmol-1: [161Tb]Tb-pDbDt, 170 MBq nmol-1: [89Zr]Zr-pDbDtDf, and the mixed radiolabeling illustrated chelation of both radionuclides in a 1 : 1 ratio. This multimodal architecture is promising as a heterometallic structure for coupling of both a diagnostic and a therapeutic radionuclide with a highly customizable core structure.

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追求治疗学:多模式架构方法。
Theranostics 是核医学的一个领域,它将相同的靶向载体和螯合系统用于诊断和治疗放射性核素,从而实现成像和治疗的一致性。这一不断发展的领域需要开发更灵活的螯合剂系统,以实现新颖的靶向策略。为此,我们实现了一种多模态结构,利用基于磷烯的核心和点击化学实现了一种灵活的、可定制的支架。六臂膦基核心可以构建六个 DTPA 螯合基团,也可以构建一组 3 :3 DTPA :DFO 螯合剂,从而分别形成两种多模式化合物 pDbDt 和 pDbDtDf。铽复合物显示出很强的发光性能,证明这种结构可以作为发光的有机天线。金属置换滴定研究证实了所需的结构以及这些结构的异金属标记能力。研究发现,这些结构在体外具有很高的热稳定性和生物稳定性。对每种化合物进行放射性标记后,发现每种化合物的摩尔活度都很高:169 MBq nmol-1:[161Tb]Tb-pDbDt;170 MBq nmol-1:[89Zr]Zr-pDbDtDf;混合放射性标记显示两种放射性核素以 1 :1 的比例螯合。这种多模式结构是一种很有前途的异金属结构,可将诊断性和治疗性放射性核素与高度可定制的核心结构耦合在一起。
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Back cover Pursuing theranostics: a multimodal architecture approach. A review on Ti3C2Tx based nanocomposites for the electrochemical sensing of clinically relevant biomarkers Back cover Introduction to Supramolecular Sensors: From Molecules to Materials
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