期刊
NUCLEAR MEDICINE AND BIOLOGY
卷 84-85, 期 -, 页码 63-72出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nucmedbio.2020.02.012
关键词
Pretargeting; Nanoparticle; Star polymer; EPR effect; PET
资金
- Australian Research Council (ARC) Centre of Excellence in Convergent Bio-Nano Science and Technology [CE140100036]
- NIHCancer Center Support Grant [P30 CA008748-48]
- NIH [R35 CA232130]
- Australian Government NHMRC [APP1132471]
Introduction: Pretargeting strategies that do not rely on the expression of molecular targets have expanded imaging and therapy options for cancer patients. Nanostars with designed multivalency and which highly accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect may therefore be the ideal vectors for the development of a passive pretargeting approach. Methods: Nanostars were synthesized, consisting of 7-8 center-cross-linked arms that were modified with transcyclooctene (TCO) using poly(ethylene glycol) (PEG) linkers of 12 or 106 monomer units or without linker. The bioorthogonal click reaction with radionuorinated 2,2'-(7-(2-(tetrazine-poly(ethyleneglycol)(11)-amino)-2-oxoethyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ([F-18]F-Tz-PEG(11)-NODA) or 2,2'-(7-(2-(tetrazine-amino)-2-oxoethyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ([F-18]F-Tz-NODA) was measured by ex vivo biodistribution studies and positron emission tomography (PET) in mice bearing tumors with high EPR characteristics. Bioorthogonal masking was performed using a tetrazine-functionalized dextran polymer (Tz-DP). Results: Highest tumor accumulation of [F-18]F-Tz-PEG(11)-NODA was observed for nanostars functionalized with TCO without linker, with a tumor uptake of 32 +/- 0.4%ID/g and a tumor-to-musde ratio of 12.8 +/- 42, tumorto-large intestine ratio of 0.5 +/- 0.3 and tumor-to-kidney ratio of 2.0 +/- 03, being significantly higher than for nanostars functionalized with TCO-PEG(12) (P< 0.05) or TCO-PEG(106) (P< 0.05). Tumor uptake and tumor-to-tissue ratios did not improve upon bioorthogonal masking with Tz-DP or when using a smaller, more lipophilic tetrazine([F-18]F-Tz-NODA). Conclusions: A pretargeting strategy was developed based on the passive delivery of TCO-functionalized nanostars. Such a strategy would allow for the imaging and treatment of tumors with apparent EPR characteristics, with high radioactive tumor doses and minimal doses to off-target tissues. (C) 2020 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据