Positron Emission Tomography Based Analysis of Long-Circulating Cross-Linked Triblock Polymeric Micelles in a U87MG Mouse Xenograft Model and Comparison of DOTA and CB-TE2A as Chelators of Copper-64

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• 作者：Andreas I. Jensen ; Tina Binderup ; Pramod Kumar EK ; Andreas Kj忙r ; Palle H. Rasmussen ; Thomas L. Andresen
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：May 12, 2014
• 年：2014
• 卷：15
• 期：5
• 页码：1625-1633
• 全文大小：443K
• 年卷期：v.15,no.5(May 12, 2014)
• ISSN：1526-4602

文摘

Copolymers of ABC-type (PEG-PHEMA-PCMA) architecture were prepared by atom transfer radical polymerization and formulated as micelles with functionalizable primary alcohols in the shell-region (PHEMA-block) to which the metal-ion chelators DOTA or CB-TE2A were conjugated. Using this micelle system we compared the in vivo stabilities of DOTA and CB-TE2A as chelators of ⁶⁴Cu in micelle nanoparticles. The coumarin polymer (PCMA-block) micelle core was cross-linked by UV irradiation at 2 W/cm² for 30 min. The cross-linked micelles were labeled with ⁶⁴Cu at room temperature for 2 h (DOTA) or 80 掳C for 3 h (CB-TE2A), giving labeling efficiencies of 60鈥?6% (DOTA) and 40鈥?7% (CB-TE2A). ⁶⁴Cu-micelles were injected into tumor-bearing mice (8 mg/kg) and PET/CT scans were carried out at 1, 22, and 46 h postinjection. The micelles showed good blood stability (T_1/2: 20鈥?6 h) and tumor uptake that was comparable with other nanoparticle systems. The DOTA micelles showed a biodistribution similar to the CB-TE2A micelles and the tumor uptake was comparable for both micelle types at 1 h (1.9% ID/g) and 22 h (3.9% ID/g) but diverged at 46 h with 3.6% ID/g (DOTA) and 4.9% ID/g (CB-TE2A). On the basis of our data, we conclude that cross-linked PEG-PHEMA-PCMA micelles have long circulating properties resulting in tumor accumulation and that DOTA and CB-TE2A ⁶⁴Cu-chelates show similar in vivo stability for the studied micelle system.