Tumor Imaging Research Articles

Organic Materials with Ultrabright Phosphorescence at Room Temperature under Physiological Conditions for Bioimaging.

In contrast to the high efficiency of room temperature phosphorescence in crystal states, the generally utilized nanoparticles of organic materials in bioimaging demonstrated sharply decreased performance by orders of magnitude under physiological conditions, badly limiting the realization of their unique advantages. This case, especially for organic red/near-infrared (NIR) phosphorescence materials, is not only the challenge present in reality but more importantly, for the theoretical problem of deeply understanding and avoiding the quenching effect by oxygen and water toward excited triplet states. Herein, thanks to the intelligent molecular design by the introduction of abundant hydrophobic chains and highly-branched structures, bright and persistent red/NIR phosphorescence under physiological conditions has been realized, which demonstrated the shielding effect towards oxygen, and strengthened the intermolecular interactions to suppress the non-radiative transitions. Accordingly, the record phosphorescence intensity of nanoparticles in bioimage, up to 8.21 ± 0.36 × 108 p s-1 cm-2 sr-1, was achieved, to realize the clear phosphorescence imaging of liver and tumors in living mice, even lymph nodes in rabbit models with high SBRs. This work afforded an efficient way to achieve the bright red/NIR phosphorescence nanoparticles, guiding their further applications in biology and medicine.

Emissive Lipid Nanoparticles as Biophotonic Contrast Agent for Site-Selective Solid Tumor Imaging in Pre-Clinical Models.

Small organic dye-based fluorescent agents are highly potent in solid tumor imaging but face challenges such as poor photostability, nonspecific distribution, low circulation, and weak tumor binding. Nanocarriers overcome these issues with better physicochemical and biological performance, particularly in cancer imaging. Among the various nanosized carriers, lipid formulations are clinically approved but yet to be designed as bright nanocontrast agents for solid tumor diagnosis without affecting surrounding tissues. Herein, indocyanine green (ICG) encapsulated targetable lipid nanoparticles (698 ICG/LNPs) as safe contrast agents (∼200 nm) have been developed and tested for solid tumor imaging and biodistribution. Our findings reveal that nanoprecipitation produces ICG-LNPs with a unique assembly, which contributes to their high brightness with improved quantum yield (3.5%) in aqueous media. The bright, optically stable (30 days) biophotonic agents demonstrate rapid accumulation (within 1 h) and prolonged retention (for up to 168 h) at the primary tumor site, with better signal intensity following a one-time dose administration (17.7 × 109 LNP per dose). Incorporated folic acid (735 folic acid/LNPs) helps in selective tumor binding and the specific biodistribution of intravenously injected nanoparticles without affecting healthy tissues. Designed targetable ICG-LNP (634 MESF) demonstrates high-contrast fluorescence and resolution from the tumor area as compared to the targetable ICG-liposomal nanoparticles (532 MESF). Various in vitro and in vivo findings reveal that the cancer diagnostic efficacy elicited by designed bright lipid nanoparticles are comparable to reported clinically accepted imaging agents. Thus, such LNPs hold translational potential for cancer diagnosis at an early stage.

Technetium-99m radiolabeling of graphene quantum dots (GQDs) as a new probe for glioblastoma tumor imaging

Purpose Cancer diagnosis involves a multi-step process. Accurate identification of the tumor, staging and development of cancer cells is crucial for selecting optimal treatments to minimize disease recurrence. Quantum dots (QDs) represent an exciting class of fluorescent nanoprobes in molecular detection and targeted tumor imaging. Materials and methods In this study, graphene quantum dots (GQDs) were synthesized by pyrolysis of citric acid (CA) as a carbon precursor under high temperatures. The morphology of the obtained GQDs was first characterized using physical (TEM and DLS) and spectroscopic (fluorescence, FTIR and UV–Vis) methods. In the following,99mTc-labeled GQDs were prepared in the presence of SnCl2.2H2O as a reducing agent between 95 and 100 °C. The biodistribution and tumor targeting efficiency of radiolabeled GQDs as a novel agent for C6 glioma tumor scintigraphy in an animal model were evaluated. Furthermore, organ uptake, human serum albumin binding and tumor accumulation were measured. Results The TEM image of the prepared GQDs showed a relatively uniform size distribution in the range of diameter 6-9 nm and spherical shape. Radiolabeled GQDs showed a radiochemical yield of >97% (n = 3). Through incubation in human serum, almost 15% of 99mTc-labeled GQDs degraded after 6 h. The amount of uptake in xenograft models of glioma C6 rats was 1.10 ± 0.36% of injection dose per gram after 1 h. The kidneys, intestinal and glioma tumor sites were observed via scintigraphy imaging. Conclusion Our data suggest that 99mTc-labeled GQDs, as a new radiotracer, efficiently accumulate in the tumor site and could be included as a radiotracer for detecting glioma tumors.

Development of a Specifically Labeled 89Zr Antibody for the Noninvasive Imaging of Tumors Overexpressing B7-H3.

B7-H3 has emerged as a promising target and potential biomarker for diagnosing tumors, evaluating treatment efficacy, and determining patient prognosis. Hu4G4 is a recombinant humanized antibody that selectively targets the extracellular domain of human B7-H3. In this study, we describe the radiolabeling of hu4G4 with the positron emission tomography (PET) emitter radionuclide zirconium 89 (89Zr) and evaluate its potency as an immuno-PET tracer for B7-H3-targeted imaging by comparing it in vitro and in vivo to [89Zr]Zr-DFO-DS-5573a using various models. The radiolabeled compound, [89Zr]Zr-desferrioxamine-hu4G4 ([89Zr]Zr-DFO-hu4G4), demonstrated a high radiochemical purity (RCP) of greater than 99% and a specific activity of 74 MBq/mg following purification. Additionally, it maintained stability in human serum albumin (HSA) and acetate buffer, preserving over 90% of its RCP after 7 days. Three cell lines targeting human B7-H3(U87/CT26-CD276/GL261-CD276) were used. Flow cytometry analysis indicated that the B7-H3-positive cells (U87/CT26-CD276/GL261-CD276) had a higher B7-H3 protein level with no expression in the B7-H3-negative cells (CT26-wt/GL261-wt) (P < 0.001). Moreover, the cellular uptake was 45.71 ± 3.78% for [89Zr]Zr-DFO-hu4G4 in CT26-CD276 cells versus only 0.93 ± 0.47% in CT26-wt cells and 30.26 ± 0.70% when [89Zr]Zr-DFO-hu4G4 in CT26-CD276 cells were blocked with 100× 8H9. The cellular uptake of [89Zr]Zr-DFO-hu4G4 was akin to that observed with [89Zr]Zr-DFO-DS-5573a with no significant differences (45.71 ± 3.78 % vs 47.07 ± 0.86 %) in CT26-CD276 cells. Similarly, the CT26-CD276 mouse model demonstrated markedly low organ uptake and elevated tumor uptake 48 h after [89Zr]Zr-DFO-hu4G4 injection. PET/CT analysis showed that the tumor-to-muscle (T/M) ratios were substantially higher compared to other imaging groups: 27.65 ± 3.17 in CT26-CD276 mice versus 11.68 ± 4.19 in CT26-wt mice (P < 0.001) and 16.40 ± 0.78 when 100× 8H9 was used to block [89Zr]Zr-DFO-hu4G4 in CT26-CD276 mice (P < 0.01) at 48 h post-injection. Additionally, the tracer showed markedly high accumulation in the tumor region (22.57 ± 3.03% ID/g), comparable to the uptake of [89Zr]Zr-DFO-DS-5573a (24.76 ± 5.36% ID/g). A dosimetry estimation study revealed that the effective dose for [89Zr]Zr-DFO-hu4G4 was 2.96 × 10-01 mSv/MBq, which falls within the acceptable range for further research in nuclear medicine. Collectively, these results indicated that [89Zr]Zr-DFO-hu4G4 was successfully fabricated and applied in B7-H3-targeted tumor PET/CT imaging, which showed excellent imaging quality and tumor detection efficacy in tumor-bearing mice. It is a promising imaging agent for identifying tumors that overexpress B7-H3 for future clinical applications.

Recent Advancements in Drug Delivery System in Lung Cancer

Eliminating the fact that the use of free pharmaceuticals in conventional dosage forms usually involves difficulties in hitting the target site at the appropriate dose after or during a correct time period, medication targeting specific organs and tissues became one of the century's most important initiatives. Thus, finding new drug delivery strategies and modes of action are lines of battle. Difficulties are still encountered with radiation therapy to accurately track the movements of lung tumors while treatments are being admitted. The development of MRI-linac hybrid system prototypes offers the possibility of real-time, ionization-free tumor imaging. This study assesses how well lung tumor tracking algorithms function on five healthy participants' cine-MRI sagittal images. The targets were vascular structures that could be seen. Lung cancer is the leading cause of mortality in the world. This is one of the heterogeneous diseases that include, at the basic level, two main subtypes: small cell lung cancer and non-small cell lung cancer. Less than 20% of patients with LC survive for 5 years on average despite recent improvements in treatment. The effectiveness of existing therapeutic techniques is impaired because of severe off-target effects and innate or acquired medication resistance. The two major types of lung cancers are SCLC and NSCLC; among these, the former is the most frequently diagnosed. Lung cancers account for the highest mortality rate due to cancer. The application of nanomedicines can partially overcome the failures that are associated with the anticancer therapies against NSCLC. One of the nanoparticle subfields that hold out much promise for better delivery while ensuring stability and sufficient bioavailability of administered anticancer medications is nanomedicine.

A DNA Molecular Logic Circuit for Precise Tumor Identification.

Tumor-associated antigens (TAAs) are not exclusively expressed in cancer cells, inevitably causing the "on target, off tumor" effect of molecular recognition tools. To achieve precise recognition of cancer cells, by using protein tyrosine kinase 7 (PTK7) as a model TAA, a DNA molecular logic circuit Aisgc8 was rationally developed by arranging H+-binding i-motif, ATP-binding aptamer, and PTK7-targeting aptamer Sgc8c in a DNA sequence. Aisgc8 output the conformation of Sgc8c to recognize PTK7 on cells in a simulated tumor microenvironment characterized by weak acidity and abundant ATP, but not in a simulated physiological environment. Through in vitro and in vivo results, Aisgc8 demonstrated its ability to precisely recognize cancer cells and, as a result, displayed excellent performance in tumor imaging. Thus, our studies produced a simple and efficient strategy to construct DNA logic circuits, opening new possibilities to develop convenient and intelligent precision diagnostics by using DNA logic circuits.

Heterogeneous Kinetics of Nanobubble Ultrasound Contrast Agent and Angiogenic Signaling in Head and Neck Cancer.

Recently developed nanobubble ultrasound contrast agents are a promising tool for imaging and drug delivery in tumors. To better understand their unusual kinetics, we implemented a novel pixel clustering analysis, which provides unique information by accounting for spatial heterogeneity. By combining ultrasound results with proteomics of the imaged tumors, we show that this analysis is highly predictive of protein expression and that specific types of nanobubble time-intensity curve are associated with upregulation of different metabolic pathways. We applied this method to study the effects of two proteins, EphB4 and ephrinB2, which control tumor angiogenesis through bidirectional juxtacrine signaling, in mouse models of head and neck cancer. We show that ephrinB2 expression by endothelial cells and EphB4 expression by cancer cells have similar effects on tumor vasculature, despite sometimes opposite effects on tumor growth. This implicates a cancer-cell-intrinsic effect of EphB4 forward signaling and not angiogenesis in EphB4's action as a tumor suppressor.

Novel 18F-Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma-2 Receptor Probes for Tumor Imaging

Novel ¹⁸F-Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma-2 Receptor Probes for Tumor Imaging

Computational modeling of tumor invasion from limited and diverse data in Glioblastoma

For diseases with high morbidity rates such as Glioblastoma Multiforme, the prognostic and treatment planning pipeline requires a comprehensive analysis of imaging, clinical, and molecular data. Many mutations have been shown to correlate strongly with the median survival rate and response to therapy of patients. Studies have demonstrated that these mutations manifest as specific visual biomarkers in tumor imaging modalities such as MRI. To minimize the number of invasive procedures on a patient and for the overall resource optimization for the prognostic and treatment planning process, the correlation of imaging and molecular features has garnered much interest. While the tumor mass is the most significant feature, the impacted tissue surrounding the tumor is also a significant biomarker contributing to the visual manifestation of mutations — which has not been studied as extensively. The pattern of tumor growth impacts the surrounding tissue accordingly, which is a reflection of tumor properties as well. Modeling how the tumor growth impacts the surrounding tissue can reveal important information about the patterns of tumor enhancement, which in turn has significant diagnostic and prognostic value. This paper presents the first work to automate the computational modeling of the impacted tissue surrounding the tumor using generative deep learning. The paper isolates and quantifies the impact of the Tumor Invasion (TI) on surrounding tissue based on change in mutation status, subsequently assessing its prognostic value. Furthermore, a TI Generative Adversarial Network (TI-GAN) is proposed to model the tumor invasion properties. Extensive qualitative and quantitative analyses, cross-dataset testing, and radiologist blind tests are carried out to demonstrate that TI-GAN can realistically model the tumor invasion under practical challenges of medical datasets such as limited data and high intra-class heterogeneity.

Value of 11C-Methionine PET Imaging in High-Grade Gliomas: A Narrative Review.

11C-Methionine (MET) is a widely utilized amino acid tracer in positron emission tomography (PET) imaging of primary brain tumors. 11C-MET PET offers valuable insights for tumor classification, facilitates treatment planning, and aids in monitoring therapeutic response. Its tracer properties allow better delineation of the active tumor volume, even in regions that show no contrast enhancement on conventional magnetic resonance imaging (MRI). This review focuses on the role of MET-PET in brain glioma imaging. The introduction provides a brief clinical overview of the problems of high-grade and recurrent gliomas. It discusses glioma management, radiotherapy planning, and the difficulties of imaging after chemoradiotherapy (pseudoprogression or radionecrosis). The mechanism of MET-PET is described. Additionally, the review encompasses the application of MET-PET in the context of primary gliomas, addressing its diagnostic precision, utility in tumor classification, prognostic value, and role in guiding biopsy procedures and radiotherapy planning.

Preclinical Evaluation of a Radiolabeled Pan-RAF Inhibitor for RAF-Specific PET/CT Imaging.

Abnormalities in the RAS-RAF signaling pathway occur in many solid tumors, leading to aberrant tumor proliferation, invasion, and metastasis. Due to the elusive pharmacology of RAS, RAF inhibitors have become the main targeted therapeutic drugs. Naporafenib (LXH-254) is a high-affinity pan-RAF inhibitor with FDA Fast Track Qualification. We sought to develop an 18F-labeled molecular probe from LXH-254 for PET imaging of tumors overexpressing RAF to noninvasively screen patients for susceptibility to targeted RAF therapy. To reduce the lipid solubility, LXH-254 was designed with triethylene glycol di(p-toluenesulfonate) (TsO-PEG3-OTs) to obtain the precursor (LXH-254-OTs) and a nucleophilic substitution reaction with 18F to obtain the tracer ([18F]F-LXH-254). [18F]F-LXH-254 exhibited good molar activity (7.16 ± 0.81 GBq/μmol), radiochemical purity (>95%), and stability. Micro-PET imaging revealed distinct radioactivity accumulation of [18F]F-LXH-254 in tumors in the imaging groups, whereas in the blocked group, the tumor radioactivity level was consistent with the background tissue, illustrating the affinity and specificity of [18F]F-LXH-254 in targeting RAF. Overall, [18F]F-LXH-254 is a promising radiotracer for screening and diagnosing patients with RAF-related disease and monitoring their treatment. This is the first attempt at using an 18F-labeled RAF-specific radiotracer.

Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA.

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.

Strategically engineered Au(I) complexes for orchestrated tumor eradication via chemo-phototherapy and induced immunogenic cell death

Cancer is a significant cause of death around the world, and for many varieties, treatment is not successful. Therefore, there is a need for the development of innovative, efficacious, and precisely targeted treatments. Here, we develop a series of Au(I) complexes (1-4) through rational manipulation of ligand structures, thereby achieving tumor cell specific targeting and orchestrated tumor eradication via chemo-phototherapy and induced immunogenic cell death. A comprehensive exploration based on in vitro and in vivo female mice experimentation shows that complex 4 exhibits proficiency in specific tumor imaging, endoplasmic reticulum targeting, and has robust therapeutic capabilities. Mechanistic elucidation indicates that the anticancer effect derives from the synergistic actions of thioredoxin reductase inhibition, highly efficient reactive oxygen species production and immunogenic cell death. This work presents a report on a robust Au(I) complex integrating three therapeutic modalities within a singular system. The strategy presented in this work provides a valuable reference for the development of high-performance therapeutic agents.

Comparison of clinical, hormonal, pathological and treatment outcomes of ectopic Cushing's syndrome by sex: results of a multicenter study.

To compare clinical and hormonal data, neuroendocrine neoplasia (NEN) localization, treatment, and survival outcomes in ectopic Cushing's syndrome (ECS) by sex. Eleven experienced centers from our country participated in this retrospective study. The clinical and hormonal features, tumor imaging, pathological results, treatment modalities, and disease courses of the patients were evaluated. 28 female and 26 male patients with ECS were compared. The mean age at diagnosis, clinical characteristics, and hormonal evaluation results were similar. However, insulin-requiring diabetes mellitus (p = 0.04) and osteoporosis with fractures were more common in males (p = 0.03). While more patients with increased DHEA-S levels than the upper limit of normal were found to be higher in females, central hypothyroidism were higher in males (p = 0.02). At the diagnosis, 36 NENs (68% of females and 69% of males) were localized. Small cell lung carcinoma was higher in males (p = 0.02), and the frequency of other NENs was not different. Curative surgery was performed on 61% of females and 46% of males. Tumor size, Ki-67 labeling index, positive ACTH immunostaining, local lymph node and distant metastasis rates were similar in both sexes. In the follow-up, the tumor became visible in 7 of 10 females and 4 of 8 males after medical treatment and/or bilateral adrenalectomy. The remission rates (65% of females, 62% of males) and NEN-related death rates (14% of females, 30% of males) were similar. While ECS has a similar disease course in many aspects in males and females, hyperglycemia and osteoporosis are more severe in males.

HMNPs@PDA-GQDs-FA as carries of gambogic acid for inhibiting VX2 tumor cells

Ellipsoidal hollow magnetic nanoparticles (HMNPs) were first synthesized through a hydrothermal method and coated with SiO2 via the Stöber method, followed by template hydrothermal synthesis using C18TMS/TEOS volume ratio for silica-shell formation. Then, the core–shell structure was grafted with graphene quantum dots (GQDs), dopamine hydrochloride (PDA), and folic acid (FA) by amide reaction to obtain HMNPs@PDA-GQDs-FA. Transmission electron microscopy, X-ray photoelectron spectroscopy, fluorescence spectroscopy, and N2 adsorption/desorption analysis confirmed the successful construction of the HMNPs@PDA-GQDs-FA nanoscale carrier–cargo composite. The carrier HMNPs@PDA-GQDs-FA had improved loading (51.63 %) and higher release (47.18 %) of gambogic acid (GA) at an acidic pH (5.7) than the release (32.23 %) at an acidic pH (7.4), showing the pH response of PDA to the surrounding environment of tumor cells. Cytotoxicity test results showed that the cell survival rate was above 95 %, indicating that the carrier–cargo had low cytotoxicity. Cell lethality was greatly improved after loading GA, and the advantages of using FA-grafted HMNPs as a targeting ligand for tumor imaging were demonstrated by SPECT imaging analysis. These results showed that HMNPs@PDA-GQDs-FA had good biocompatibility and could be used for the treatment of VX2 tumors after loading GA.

WazaGaY: An Innovative Aza-BODIPY-Derived Near-Infrared Fluorescent Probe for Enhanced Tumor Imaging.

Aza-BODIPYs represent a class of fluorophores in which the π-conjugated system is rigidified and stabilized by a boron atom. A promising strategy to enhance their fluorescence properties involves replacing the boron atom with a metal ion. Here, we describe the synthesis and characterization of a water-soluble derivative where the metal is a gallium(III) ion, termed WazaGaY (water-soluble aza-GaDIPY). Water solubility is ensured by two ammonium substituents, inducing a bathochromic shift and a significant increase in quantum yield compared to that of the dimethylamino analog. The cellular behavior of WazaGaY-1 was observed across different tumor cells. In vivo, the distribution and safety profiles were determined, and tumor uptake was assessed in various tumor types. Following intravenous injection, WazaGaY-1 enabled clear discrimination of tumors engrafted subcutaneously in mice with high tumor-to-muscle ratios (ranging from 7 to 20), even in the absence of specific conjugation. Its potential as a contrast agent for fluorescence-guided surgery was confirmed.

Monte Carlo simulation of spatial frequency domain imaging for breast tumors during compression.

Near-infrared optical imaging methods have shown promise for monitoring response to neoadjuvant chemotherapy (NAC) for breast cancer, with endogenous contrast coming from oxy- and deoxyhemoglobin. Spatial frequency domain imaging (SFDI) could be used to detect this contrast in a low-cost and portable format, but it has limited imaging depth. It is possible that local tissue compression could be used to reduce the effective tumor depth. To evaluate the potential of SFDI for therapy response prediction, we aim to predict how changes to tumor size, stiffness, and hemoglobin concentration would be reflected in contrast measured by SFDI under tissue compression. Finite element analysis of compression on an inclusion-containing soft material is combined with Monte Carlo simulation to predict the measured optical contrast. When the effect of compression on blood volume is not considered, contrast gain from compression increases with the size and stiffness of the inclusion and decreases with the inclusion depth. With a model of reduction of blood volume from compression, compression reduces imaging contrast, an effect that is greater for larger inclusions and stiffer inclusions at shallower depths. This computational modeling study represents a first step toward tracking tumor changes induced by NAC using SFDI and local compression.

A dual-responsive fluorescent probe for cellular hypoxia and tumor imaging based on nitroreductase and viscosity synergy

Nitroreductase (NTR), an enzyme that operates within the cytoplasm, relies on flavin mononucleotide or flavin adenine dinucleotide for its activity. In tumor cells, hypoxic conditions often lead to an increase in NTR levels. Consequently, the development of fluorescent probes capable of detecting NTR activity is crucial for the monitoring of hypoxia in biological systems. This study presents the one-step synthesis of a near-infrared fluorescent probe, DSM-NO2. The probe was highly sensitive to NTR and caused a fluorescence enhancement by 50-fold, with a detection limit as low as 1 ng/mL. Under hypoxic conditions in tumor cells, not only does NTR increase, but the cellular viscosity also rises. In high-viscosity environments, the fluorescence enhancement could reach up to 220-fold, and the detection limit could be further reduced to 55 pg/mL. The reaction mechanism was thoroughly investigated using mass spectrometry, molecular docking, and theoretical calculations. Moreover, the probe was successfully applied in the real-time monitoring and visualization analysis of NTR during the growth of Escherichia coli and in the hypoxic state of cancer cells. Additionally, through nebulized inhalation, the probe was successfully employed for in situ fluorescent imaging studies in a murine model of lung cancer.

Synthesis of Antifouling Poly(ethylene glycol) Brushes via "Grafting to" Approach for Improved Biodistribution.

Polyethylene glycol (PEG) modification of materials has been identified to mitigate the challenge of biofouling. However, the practical application of PEGylation has been hampered by a low PEGylation density on the material surface. Therefore, developing efficient strategies to promote the PEGylation density is crucial. In this study, PEG brushes (PBs) with various structures were synthesized and their physicochemical properties and biomedical applications were investigated. Compared to benzaldehyde (BA), o-phthalaldehyde (OPA) exhibited higher reactivity with amine groups, resulting in increased grafting density (as high as 96.3%) and improved antifouling properties of PEG brushes. Bottlebrushes fabricated by PEG-OPA and polylysine demonstrated a prolonged circulation time in blood and enhanced potential for magnetic resonance imaging of tumors. Furthermore, the rigidity of the backbone was found to be crucial for the antifouling properties of PEG brushes both in vitro and in vivo. These findings are significant and provide valuable insights into designing biomaterials with superior antifouling performance.

Novel 99mTc-Labeled Mannose Derivative as a Highly Promising Single Photon Emission Computed Tomography Probe for Tumor Imaging.

18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) has been the most used positron emission tomography imaging agent for clinical applications. Single photon emission computed tomography (SPECT) imaging is cheaper and used more widely for diagnostic use, but there is no SPECT tumor imaging agent for clinical applications comparable to [18F]FDG. Mannose is a C2 epimer of glucose and can also be transported into tumor cells via glucose transporters (GLUTs). To develop a novel SPECT tumor imaging agent with satisfactory tumor uptake and tumor/nontarget ratios, here a mannose derivative (CN7DM) was synthesized and radiolabeled with technetium-99m to prepare [99mTc]Tc-CN7DM. The six-coordinated structure of [99mTc]Tc-CN7DM was confirmed by the corresponding rhenium compound (Re-CN7DM). [99mTc]Tc-CN7DM was transported into cancer cells via GLUTs and may be trapped in the cancer cells by electrostatic attraction. The probe exhibited high uptake in tumors and low uptake in nontarget tissues in mice bearing different tumors, indicating that [99mTc]Tc-CN7DM exhibited promising potential for SPECT tumor imaging and warranted further clinical investigation.