SPECT/CT imaging of chemotherapy-induced tumor apoptosis using ^99mTc-labeled dendrimer-entrapped gold nanoparticles

Abstract

Non-invasive imaging of apoptosis in tumors induced by chemotherapy is of great value in the evaluation of therapeutic efficiency. In this study, we report the synthesis, characterization, and utilization of radionuclide technetium-99m (^99mTc)-labeled dendrimer-entrapped gold nanoparticles (Au DENPs) for targeted SPECT/CT imaging of chemotherapy-induced tumor apoptosis. Generation five poly(amidoamine) (PAMAM) dendrimers (G5.NH₂) were sequentially conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), polyethylene glycol (PEG) modified duramycin, PEG monomethyl ether, and fluorescein isothiocyanate (FI) to form the multifunctional dendrimers, which were then utilized as templates to entrap gold nanoparticles. Followed by acetylation of the remaining dendrimer surface amines and radiolabeling of ^99mTc, the SPECT/CT dual mode nanoprobe of tumor apoptosis was constructed. The developed multifunctional Au DENPs before and after ^99mTc radiolabeling were well characterized. The results demonstrate that the multifunctional Au DENPs display favorable colloidal stability under different conditions, own good cytocompatibility in the given concentration range, and can be effectively labeled by ^99mTc with high radiochemical stability. Furthermore, the multifunctional nanoprobe enables the targeted SPECT/CT imaging of apoptotic cancer cells in vitro and tumor apoptosis after doxorubicin (DOX) treatment in the established subcutaneous tumor model in vivo. The designed duramycin-functionalized Au DENPs might have the potential to be employed as a nanoplatform for the detection of apoptosis and early tumor response to chemotherapy.

Keywords:

• Dendrimers
• duramycin
• apoptosis
• chemotherapy
• SPECT/CT imaging

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research is financially supported by the National Natural Science Foundation of China [81401440, 81671712, 21773026, and 81761148028], the Science and Technology Commission of Shanghai Municipality [17540712000], and the Fundamental Research Funds for the Central Universities. J. Zhu thanks the support from the Natural Science Foundation for Colleges and Universities in Jiangsu Province [17KJB350005]. L. Zhao thanks the support from the Shanghai Sailing Program [16YF1409300].