Organic Radical Contrast Agents Based on Polyacetylenes Containing 2,2,6,6-Tetramethylpiperidine 1-Oxyl (TEMPO): Targeted Magnetic Resonance (MR)/Optical Bimodal Imaging of Folate Receptor Expressing HeLa Tumors in Vitro and in Vivo(a)

Lixia Huang; Chenggong Yan; Danting Cui; Yichen Yan; Xiang Liu; Xinwei Lu; Xiangliang Tan; Xiaodan Lu; Jun Xu; Yikai Xu; Ruiyuan Liu

doi:10.1002/mabi.201400403

Organic Radical Contrast Agents Based on Polyacetylenes Containing 2,2,6,6-Tetramethylpiperidine 1-Oxyl (TEMPO): Targeted Magnetic Resonance (MR)/Optical Bimodal Imaging of Folate Receptor Expressing HeLa Tumors in Vitro and in Vivo(a)

Macromol Biosci. 2015 Jun;15(6):788-98. doi: 10.1002/mabi.201400403. Epub 2015 Feb 13.

Authors

Lixia Huang^{1

2}, Chenggong Yan¹, Danting Cui¹, Yichen Yan³, Xiang Liu¹, Xinwei Lu³, Xiangliang Tan¹, Xiaodan Lu¹, Jun Xu⁴, Yikai Xu⁵, Ruiyuan Liu⁶

Affiliations

¹ Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
² Department of Radiology, Guangdong Provincial Traditional Chinese Medical Hospital, Guangzhou, 510120, China.
³ School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
⁴ Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
⁵ Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. [email protected].
⁶ School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. [email protected].

PMID: 25677802
DOI: 10.1002/mabi.201400403

Abstract

Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.

Keywords: MRI; contrast agent; folic acid; optical imaging; organic radicals.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Contrast Media* / chemistry
Contrast Media* / pharmacology
Cyclic N-Oxides* / chemistry
Cyclic N-Oxides* / pharmacology
Female
Folate Receptors, GPI-Anchored / biosynthesis*
HeLa Cells
Humans
Magnetic Resonance Imaging*
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Imaging*
Neoplasm Proteins / biosynthesis*
Neoplasms / diagnostic imaging
Neoplasms / metabolism
Radiography

Substances

Contrast Media
Cyclic N-Oxides
Folate Receptors, GPI-Anchored
Neoplasm Proteins
TEMPO