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.

131I‐Labeled Multifunctional Polyphosphazene Nanospheres for SPECT Imaging‐Guided Radiotherapy of Tumors

“…Instant thin layer chromatography (ITLC) was used to analyze the labeling efficiency and radiostability of the 131 I‐labeled materials. The efficiency of 131 I labeling onto PNS.NHAc‐HPAO‐PS and PEI.NHAc‐HPAO‐PS was determined to be 76.05 ± 3.75% and 55.3 ± 1.13%, respectively, which are comparable to those reported in the literature . In other words, the doses of PNS.NHAc‐HPAO( 131 I)‐PS and PEI.NHAc‐HPAO( 131 I)‐PS were presented as 2.81 and 2.03 MBq µg −1 , respectively.…”

Chlorotoxin peptide-functionalized polyethylenimine-entrapped gold nanoparticles for glioma SPECT/CT imaging and radionuclide therapy

“…In our recent work, we developed CTX-conjugated multifunctional dendrimers labeled with radionuclides for targeted imaging and therapy of glioma [38]. Furthermore, we have demonstrated that radionuclide-labeled dendrimers can be used to entrap gold nanoparticles (Au NPs) for tumor dual mode imaging applications, such SPECT/CT and SPECT/MR imaging [39–41]. The previous successes of dendrimer-based multifunctional nanosystems and the unique biological properties of CTX, prompted our investigation of dendrimers as a BBB-penetrating nanoplatform for the dual mode imaging and radionuclide therapy of glioma.…”

Gold Nanoparticles and Nanorods in Nuclear Medicine: A Mini Review

“…Duramycin has a high specificity in recognizing the phospholipid phosphatidylserine (PS), which is present on the outer surface of the cellular membrane of apoptotic cells. The results show that SPECT images of apoptotic C6 cells treated with the 99mTc-duramycin-Au DENPs are much brighter than those of apoptotic C6 cells treated with the 99m Tc-duramycin-Au DENPs [128].…”

“…A recent study aimed to evaluate the synthesis, characterization, and use of 99m Tc-labeled dendrimer-entrapped AuNPs ( 99m Tc-Au DENPs) for targeted SPECT/CT imaging of chemotherapy-induced tumor apoptosis [128]. Indeed, 99m Tc-Au DENPs allowed the targeted imaging of apoptotic cancer cells in vitro and of tumor apoptosis after doxorubicin treatment in nude mice bearing C6 glioma cells and xenografted tumors.…”