Department of Chemistry, Radiochemistry, University of Helsinki, Helsinki FI-00014, Finland.
Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
Nucl Med Biol. 2022 Nov-Dec;114-115:151-161. doi: 10.1016/j.nucmedbio.2022.05.004. Epub 2022 May 24.
Pretargeted PET imaging allows the use of radiotracers labeled with short-living PET radionuclides for tracing drugs with slow pharmacokinetics. Recently, especially methods based on bioorthogonal chemistry have been under intensive investigation for pretargeted PET imaging. The pharmacokinetics of the radiotracer is one of the factors that determine the success of the pretargeted strategy. Here, we report synthesis and biological evaluation of two Ga-labeled tetrazine (Tz)-based radiotracers, [Ga]Ga-HBED-CC-PEG-Tz ([Ga]4) and [Ga]Ga-DOTA-PEG-Tz ([Ga]6), aiming for development of new tracer candidates for pretargeted PET imaging based on the inverse electron demand Diels-Alder (IEDDA) ligation between a tetrazine and a strained alkene, such as trans-cyclooctene (TCO). Excellent radiochemical yield (RCY) was obtained for [Ga]4 (RCY > 96%) and slightly lower for [Ga]6 (RCY > 88%). Radiolabeling of HBED-CC-Tz proved to be faster and more efficient under milder conditions compared to the DOTA analogue. The two tracers exhibited excellent radiolabel stability both in vitro and in vivo. Moreover, [Ga]4 was successfully used for radiolabeling two different TCO-functionalized nanoparticles in vitro: Hepatitis E virus nanoparticles (HEVNPs) and porous silicon nanoparticles (PSiNPs).
基于靶向前置的 PET 成像允许使用放射性示踪剂标记短半衰期的正电子放射性核素来追踪具有缓慢药代动力学的药物。最近，特别是基于生物正交化学的方法，已经成为基于靶向前置的 PET 成像的研究热点。放射性示踪剂的药代动力学是决定基于靶向前置策略成败的因素之一。在这里，我们报告了两种基于叠氮化物（Tz）的镓标记放射性示踪剂[Ga]Ga-HBED-CC-PEG-Tz ([Ga]4)和[Ga]Ga-DOTA-PEG-Tz ([Ga]6)的合成和生物学评价，旨在开发基于反电子需求 Diels-Alder (IEDDA) 键合的新型基于靶向前置的 PET 成像示踪剂候选物，该键合发生在 Tz 和刚性烯烃（如反式环辛烯（TCO））之间。[Ga]4 的放射化学产率（RCY）非常高（RCY>96%），[Ga]6 的 RCY 略低（RCY>88%）。与 DOTA 类似物相比，HBED-CC-Tz 的放射性标记在更温和的条件下更快、更有效。两种示踪剂在体外和体内均表现出优异的放射性标记稳定性。此外，[Ga]4 成功地用于体外标记两种不同的 TCO 功能化纳米粒子：戊型肝炎病毒纳米粒子（HEVNP）和多孔硅纳米粒子（PSiNP）。
