Molecular imaging techniques apply sophisticated technologies to monitor, directly or indirectly, the spatiotemporal distribution of molecular or cellular processes for biomedical, diagnostic, or therapeutic purposes. For example, Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) imaging, the most representative modalities of molecular imaging, enable earlier and more accurate diagnosis of cancer and cardiovascular diseases. New possibilities for noninvasive molecular imaging in vivo have emerged with advances in bioorthogonal chemistry. For example, tetrazine-related Inverse Electron Demand Diels-Alder (IEDDA) reactions can rapidly generate short-lived radioisotope probes in vivo that provide strong contrast for SPECT and PET. Here, we review pretargeting strategies for molecular imaging and novel radiotracers synthesized via tetrazine bioorthogonal chemistry. We systematically describe advances in direct radiolabeling and pretargeting approaches in SPECT and PET using metal and nonmetal radioisotopes based on tetrazine bioorthogonal reactions, and we discuss prospects for the future of such contrast agents.

分子成像技术应用复杂的技术来直接或间接地监测分子或细胞过程的时空分布，以达到生物医学，诊断或治疗目的。例如，单光子发射计算机断层扫描（SPECT）和正电子发射断层扫描（PET）成像是分子成像的最具代表性的形式，可以更早，更准确地诊断癌症和心血管疾病。随着生物正交化学的发展，体内无创分子成像的新可能性已经出现。例如，与四嗪相关的逆电子需量Diels-Alder（IEDDA）反应可以在体内迅速产生寿命短的放射性同位素探针，从而为SPECT和PET提供强对比。这里，我们审查了分子成像和通过四嗪生物正交化学合成的新型放射性示踪剂的预靶向策略。我们系统地描述了基于四嗪生物正交反应的金属和非金属放射性同位素在SPECT和PET中直接放射性标记和预靶向方法的进展，并讨论了这类造影剂的未来前景。