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Abstract Multimodal imaging unfolds as an innovative approach that synergistically employs a spectrum of imaging techniques either simultaneously or sequentially. The integration of computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and optical imaging (OI) results in a comprehensive and complementary understanding of complex biological processes. This innovative approach combines the strengths of each method and overcoming their individual limitations. By harmoniously blending data from these modalities, it significantly improves the accuracy of cancer diagnosis and aids in treatment decision-making processes. Nanoparticles possess a high potential for facile functionalization with radioactive isotopes and a wide array of contrast agents. This strategic modification serves to augment signal amplification, significantly enhance image sensitivity, and elevate contrast indices. Such tailored nanoparticles constructs exhibit a promising avenue for advancing imaging modalities in both preclinical and clinical setting. Furthermore, nanoparticles function as a unified nanoplatform for the co-localization of imaging agents and therapeutic payloads, thereby optimizing the efficiency of cancer management strategies. Consequently, radiolabeled nanoparticles exhibit substantial potential in driving forward the realms of multimodal imaging and theranostic applications. This review discusses the potential applications of molecular imaging in cancer diagnosis, the utilization of nanotechnology-based radiolabeled materials in multimodal imaging and theranostic applications, as well as recent advancements in this field. It also highlights challenges including cytotoxicity and regulatory compliance, essential considerations for effective clinical translation of nanoradiopharmaceuticals in multimodal imaging and theranostic applications. Graphical Abstract

Nanotechnology-based drug delivery platforms have emerged as one of the promising approaches for the diagnosis and treatment of cancers. Furthermore, significant advancements have been achieved in the development of nanoparticle-antibody conjugates for applications in tumor imaging and immunoassays. Without a doubt, the diagnostic insight garnered from these nanoprobes will prove invaluable in determining rational therapeutic strategies. In the current experiment, we developed a breast cancer imaging probe utilizing graphene quantum dots, these quantum dots were conjugated with pembrolizumab (GQDs–pembrolizumab), a human monoclonal antibody (mAb) targeting the immune checkpoint programmed death receptor (PD-1) and its programmed death ligand-1 (PD-L1). Various techniques were employed for characterization, encompassing transmission electron microscopy (TEM), element mapping, atomic force microscopy (AFM), Fourier-transform infrared spectroscopy, and circular dichroism (CD) spectroscopy. The toxicity of nanoconjugate was evaluated using the MTT assay on HEK-293 and 4T1 cell lines. Subsequently, the synthesized nanoconjugate was radiolabeled with Technetium-99m (99mTc) to produce 99mTc-GQDs–pembrolizumab. Biodistribution and SPECT imaging were conducted to assess the pharmacokinetics and targeting efficacy of the 99mTc-GQDs–pembrolizumab in a BALB/c mouse model bearing with 4T1 tumors. The high Radiochemical purity (RCP > 95 %) and satisfactory in vitro stability demonstrate the significant potential of GQDs–pembrolizumab to form complexes with Technetium-99m. The findings from imaging and biodistribution studies demonstrated the high activity of 99mTc-GQDs–pembrolizumab at the tumor site (8.4 %ID/g), attributed to the presence of the PD-1 receptor. Furthermore, the increased radiotracer uptake was evident in the liver and spleen, both being lymphoid tissues. The suitable properties and behavior of 99mTc-GQDs–pembrolizumab suggest that it holds promise as a novel probe for the development of radiopharmaceutical-based immune checkpoint monoclonal antibodies. Additionally, it has the potential to facilitate immunotherapy for treating a wide range of cancers.

Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski′s rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two π-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue.

Understanding the geometry, electronic properties of non-steroidal anti-inflammatory drugs (NSAIDs) and the nature of their interactions with human cyclooxygenase-2 (COX-2) is important in development and design of novel NSAIDs. In this paper, B3LYP/6-311++G (d,p) level of theory was applied to assess acidity of NSAIDs in the gas phase. Subsequently, the role of intramolecular hydrogen bond on acidity of these compounds was confirmed by means of natural bond orbital (NBO) and quantum theory of atoms in molecules analyses (QTAIM). Furthermore, by applying the polarized continuum model (PCM) at the B3LYP/6-311++G(d,p) level, the pKa value of NSAIDs in aqueous solution has been calculated. The maximum error was found to be less than 0.1 pKa unit in comparison with the experimental value. This protocol can be used as a tool to predict pKa values of NSAIDs in future studies. In the last step, attempts have been made to generate a functional model of the structure of human COX-2 enzyme by means of homology modeling to gain more insight to the nature of interactions between NSAIDs and the active site of this COX-2 enzyme by docking studies. In addition, a mean binding energy for each drug was estimated based on its ionization ratio.

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Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two p-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue. [ABSTRACT FROM AUTHOR]

Density functional theory method and B3LYP/6-311++G(d,p) level of theory were used to determine the acidity of alkyl and polyolalkyl in the gas and solution (H2O, DMSO, and CH3CN) phase. Polarized continuum model was applied to calculate p Ka values of alkyl and polyolalkyl . A comparison between acidity of alkyl and polyolalkyl in the gas and solution phase indicates that the acidity strength of polyolalkyl enhances with the increase of the cooperativity effect of hydrogen bonds in polyolalkyl . Natural bond orbital and quantum theory of atoms in molecules analyses also confirm the role of cooperativity effect on the acidity of polyolalkyl . Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]