Inverse electron demand Diels-Alder click chemistry for pretargeted PET imaging and radioimmunotherapy.
Inverse electron demand Diels-Alder click chemistry for pretargeted PET imaging and radioimmunotherapy.
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DOI：
10.1038/s41596-021-00540-2
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发表时间：
2021-07
期刊：
影响因子：
14.8
通讯作者：
Zeglis BM
中科院分区：
文献类型：
--
作者：
Sarrett SM;Keinänen O;Dayts EJ;Dewaele-Le Roi G;Rodriguez C;Carnazza KE;Zeglis BM
放射标记抗体已显示出作为核成像和癌症放射治疗工具的前景，但放射免疫偶联物的长循环时间可能导致对健康组织的高辐射剂量。为了避免这个问题，我们开发了一种正电子发射断层扫描（PET）成像和放射免疫治疗（RIT）的方法，该方法基于抗体到达体内目标后的放射性标记。这种体内预靶向策略是基于四嗪（Tz）和反式环烯（TCO）之间快速和生物正交的反电子需求diols - alder反应。与直接标记的放射免疫偶联物相比，使用tco修饰的抗体与含tz的放射配体结合的预靶向PET成像和放射免疫治疗在靶组织中产生高活性浓度，并减少对健康器官的辐射剂量。本文描述了如何制备tco修饰的抗体（huA33-TCO）以及如何合成两个含z的放射性配体：一个以正电子发射的放射性金属铜-64 （[64Cu]Cu-SarAr-Tz）标记，一个以β发射的放射性镧系元素镥-177 （[177Lu]Lu-DOTA-PEG7-Tz）标记。我们还提供了一个详细的描述预靶向PET和预靶向放射免疫治疗（PRIT）在人类大肠癌小鼠模型中的实验。要成功地执行这一方案，需要在辐射安全和处理实验室小鼠方面进行适当的培训。
Radiolabeled antibodies have shown promise as tools for both the nuclear imaging and endoradiotherapy of cancer, but the protracted circulation time of radioimmunoconjugates can lead to high radiation doses to healthy tissues. To circumvent this issue, we have developed an approach to positron emission tomography (PET) imaging and radioimmunotherapy (RIT) predicated on radiolabeling the antibody after it has reached its target within the body. This in vivo pretargeting strategy is based on the rapid and bioorthogonal inverse electron demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO). Pretargeted PET imaging and radioimmunotherapy using TCO-modified antibodies in conjunction with Tz-bearing radioligands produce high activity concentrations in target tissues as well as reduced radiation doses to healthy organs compared to directly-labeled radioimmunoconjugates. Herein, we describe how to prepare a TCO-modified antibody (huA33-TCO) as well as how to synthesize two Tz-bearing radioligands: one labeled with the positron-emitting radiometal copper-64 ([64Cu]Cu-SarAr-Tz) and one labeled with the β-emitting radiolanthanide lutetium-177 ([177Lu]Lu-DOTA-PEG7-Tz). We also provide a detailed description of pretargeted PET and pretargeted radioimmunotherapy (PRIT) experiments in a murine model of human colorectal carcinoma. Proper training in both radiation safety and the handling of laboratory mice is required for the successful execution of this protocol.
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影响因子：
4.1
作者：
Gupta A;Mishra A;Puri N
通讯作者：
Puri N
影响因子：
3.2
作者：
Kramer K;Pandit-Taskar N;Humm JL;Zanzonico PB;Haque S;Dunkel IJ;Wolden SL;Donzelli M;Goldman DA;Lewis JS;Lyashchenko SK;Khakoo Y;Carrasquillo JA;Souweidane MM;Greenfield JP;Lyden D;De Braganca KD;Gilheeney SW;Larson SM;Cheung NV
通讯作者：
Cheung NV
DOI：
10.2967/jnumed.115.163824
发表时间：
2016-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Houghton JL;Zeglis BM;Abdel-Atti D;Sawada R;Scholz WW;Lewis JS
通讯作者：
Lewis JS
影响因子：
3.2
作者：
Carroll, Laurence;Evans, Helen L.;Spivey, Alan C.
通讯作者：
Spivey, Alan C.
影响因子：
3.2
作者：
Keinänen O;Fung K;Pourat J;Jallinoja V;Vivier D;Pillarsetty NK;Airaksinen AJ;Lewis JS;Zeglis BM;Sarparanta M
通讯作者：
Sarparanta M