^99mTc-Labeled Multifunctional Low-Generation Dendrimer-Entrapped Gold Nanoparticles for Targeted SPECT/CT Dual-Mode Imaging of Tumors

Abstract

Development of cost-effective and highly efficient nanoprobes for targeted tumor single-photon emission computed tomography (SPECT)/computed tomography (CT) dual-mode imaging remains a challenging task. Here, multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) modified with folic acid (FA) and labeled with (99m)Tc were synthesized for targeted dual-mode SPECT/CT imaging of tumors. Generation 2 (G2) poly(amidoamine) (PAMAM) dendrimers (G2-NH2) conjugated with cyclic diethylenetriamine pentaacetic anhydride (cDTPAA) via an amide linkage and FA via a spacer of polyethylene glycol (PEG) were used for templated synthesis of Au core NPs, followed by labeling of (99m)Tc via chelation. The thus created multifunctional Au DENPs were well-characterized. It is shown that particles with an average Au core diameter of 1.6 nm can be dispersed in water, display stability under different conditions, and are cytocompatible in the studied concentration range. Further results demonstrate that the multifunctional nanoprobe is able to be utilized for targeted SPECT/CT dual-mode imaging of cancer cells having FA receptor (FAR)-overexpression in vitro and the established subcutaneous tumor model in vivo within a time frame up to 4 h. The formed multifunctional Au DENPs synthesized using dendrimers of low-generation may be employed as an effective and economic nanoprobe for SPECT/CT imaging of different types of FAR-expressing tumors.

A Smart Responsive Dual Aptamers‐Targeted Bubble‐Generating Nanosystem for Cancer Triplex Therapy and Ultrasound Imaging

“…Diagnosis is a prerequisite for treatment. Among available diagnostic modalities such as computed tomography, positron emission tomography, fluorescence imaging, and magnetic resonance imaging, ultrasound imaging has comparative advantages over others including being noninvasive and providing real‐time imaging . Furthermore, US imaging is a convenient and inexpensive solution for patients .…”

99mTc-labelled multifunctional polyethylenimine-entrapped gold nanoparticles for dual mode SPECT and CT imaging

“…The Au PENPs were labelled with 99m Tc through DTPA ligands according to protocols described in the literature [25,26].…”

“…On the other hand, 99m Tc is an ideal radioisotope for SPECT imaging due to its favourable lowenergy c-ray (140 keV), appropriate half-life (6.02 h), low cost and commercial availability. Numerous 99m Tc-labelled NPs have been developed as molecular probes for SPECT imaging applications in cancer, sentinel lymph node (SLN) and other biological systems [24][25][26][27]. Notably, unique features of nanotechnology allow integrating multiple imaging modalities in one particle system to form multifunctional NPs for multimodal imaging [28][29][30].…”

PAMAM Dendrimer‐Based Nanodevices for Nuclear Medicine Applications

“…Due to the good biocompatibility after appropriate surface modification (e.g., acetylation or PEGylation), non‐immunogenicity, and abundant peripheral functional groups, poly(amidoamine) (PAMAM) dendrimers have been covalently conjugated with various functional moieties including targeting ligands, imaging agents, drug molecules, and radionuclides for different biomedical applications . For instance, chelators such as diethylenetriaminepentaacetic acid (DTPA), 6‐hydrazinonicotinyl,20c tetraazacyclododecanetetraacetic acid (DOTA), and 2,2′‐(7‐(2‐((2,5‐dioxopyrrolidin‐1‐yl)oxy)‐2‐oxoethyl)‐1,4,7‐triazonane‐1,4‐diyl)diacetic acid (NOTA) can be conjugated onto the surface of PAMAM dendrimers to label technetium‐99m ( 99m Tc) and 64 Cu for SPECT and PET12b,25 imaging, respectively. The phenol groups of 3‐(4′‐hydroxyphenyl)propionic acid‐OSu (HPAO) can be modified onto the PAMAM dendrimer surface to label iodine‐131( 131 I) for SPECT imaging‐guided RT of tumors 19b,26.…”