Targeted Imaging Agents Research Articles

Abstract B026: Development of a novel theranostic agent targeting MET in lung and head and neck cancer

Abstract Background: The mesenchymal transcript factors is a receptor tyrosine kinase that when dysregulated or overexpressed can stimulate oncogenesis. Alterations in MET are found in 5% of non-small cell lung cancer but are also found in head and neck cancer and in cancers resistant to tyrosine kinase inhibitors targeting other oncogenic drivers. Our objective is to evaluate a novel, camelid-derived, MET binding antibody as a potential theranostic agent used in MET expressing cancers. Methods: The anti-MET VHH camelid antibody, 1E7-Fc, was identified from a phage display library. Binding to human MET was assessed via serially diluted ELISA analysis and bio-Layer interferometry. Western blot and qRT-PCR analysis was used to assess MET and p-MET expression in established multiple lung cancer (EBC-1 and UW-Lung-21) and head and neck cancer (Detroit 562, UM-SCC47, and UPCI:SCC90) cell lines where inhibition was compared to treatment with the MET inhibitor, capmatinib. Binding affinity and internalization of 1E7-Fc to these cell lines was assessed via flow cytometry and immunofluorescence. EC50 assays were performed to measure the effects of 1E7-Fc on cell viability. Bioconjugation of 89Zr and 177Lu enabled tumor uptake imaging in xenograft models using PET/CT and SPECT imaging, respectively. The efficacy of [89Zr]Zr-1E7-Fc as an imaging agent targeting MET expression in vivo was investigated through PET/CT imaging, region of interest (ROI) image analysis, and ex vivo activity. Results: 1E7-Fc demonstrates a high binding affinity for human MET. Binding to MET expressing cell lines correlated to levels of MET expression and was seen even in cells resistant to MET inhibitor capmatinib. 1E7-Fc did not cause disrupt MET signaling and did not impair cell proliferation. [89Zr]Zr-1E7-Fc demonstrated rapid localization and high tumor uptake in EBC-1, UW-Lung-21, and Detroit 562 xenografts with rapid clearance from circulatory systems as tumor to blood ratios were 2.7, 2.5, and 1.8 forty-eight hours post injection, respectively.1E7-Fc was successfully labeled with 177Lu and imaged by SPECT. Conclusions: Our preclinical findings indicate that the camelid antibody MET-1E7-Fc has potential as an imaging agent for high MET-expressing cancers. Further studies are needed to assess the therapeutic response to 177Lu-conjugated antibodies and to translate these results to patients. Citation Format: Rachel L. Minne, Natalie Y. Luo, Caroline M. Mork, Madalynn R. Wopat, Jayden L. West, Jessica E. Griffin, Karla Esbona, Saahil Javeri, Kwangok P. Nickel, Reinier Hernandez, Aaron M. LeBeau, Randall J. Kimple, Andrew M. Baschnagel. Development of a novel theranostic agent targeting MET in lung and head and neck cancer. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B026.

Preoperative [18F]fluoro-PEG-folate PET/CT in advanced stage epithelial ovarian cancer: A safety and feasibility study

PurposeThe selection for either primary or interval cytoreductive surgery (CRS) in patients with epithelial ovarian cancer (EOC) is currently based on imaging techniques like computed tomography (CT), [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET), diffusion-weighted magnetic resonance imaging (DW-MRI) and/or diagnostic laparoscopy, but these have limitations. Folate receptor (FR)-targeted PET/CT imaging, using [18F]fluoro-PEG-folate, could improve preoperative assessment, potentially reducing unnecessary laparotomies. This paper presents the first experience with [18F]fluoro-PEG-folate PET/CT imaging in advanced stage EOC, focusing on safety, tolerability, and feasibility for reflecting the extent of disease. MethodsTolerability and safety were monitored after administration of the [18F]fluoro-PEG-folate tracer by measurements of vital function parameters (blood pressure, heart rate, peripheral oxygen saturation, respiratory rate, and temperature). In addition, (serious) adverse events were recorded. Disease burden was quantified using the Peritoneal Cancer Index (PCI) score on preoperative [18F]fluoro-PEG-folate PET/CT and during surgery. PCI scores were compared with intraoperative findings, considering histopathologic results as the gold standard. Tissue specimens were stained for FRα and FRβ. Relative uptake of the radiotracer by EOC lesions and other tissues was quantified using body weighted standardized uptake values (SUV). ResultsThe study was terminated prematurely during the interim analysis after inclusion of eight patients of whom five had completed the study protocol. Although [18F]fluoro-PEG-folate demonstrated safety, efficacy for tumor-specific imaging was limited. Despite clear FRα overexpression, low tracer uptake was observed in EOC lesions, contrasting with high uptake in healthy tissues, posing challenges in specificity and accurately assessing tumor burden. ConclusionsOverall, while [18F]fluoro-PEG-folate was well-tolerated, its clinical utility in the preoperative assessment of the extent of disease in EOC was limited. This highlights the need for further research in developing targeted imaging agents for optimal detection of EOC metastases.Trial registration: Clinicaltrials.gov, NCT05215496. Registered 31 January 2022.

Signature of click chemistry in exosome modification for cancer therapeutic

AbstractExosomes, small extracellular vesicles secreted by cells, have gained attention as potential therapeutic agents due to their natural ability to deliver biomolecules and traverse biological barriers. However, their limited targeting specificity and payload capacity necessitate modifications for improved therapeutic efficacy. Click chemistry, known for its high specificity, efficiency, and mild reaction conditions, offers an innovative solution for modifying exosomal surfaces. This technique enables precise attachment of targeting ligands, imaging agents, and therapeutic molecules, enhancing the targeting, delivery, and overall effectiveness of exosome‐based therapies. By addressing cancer heterogeneity, click chemistry‐modified exosomes can target diverse cancer cell populations within tumors, improving treatment specificity and reducing drug resistance. The development of copper‐free click chemistry, such as strain‐promoted azide‐alkyne cycloaddition (SPAAC), minimizes toxicity, ensuring biocompatibility and safety. As research progresses, this approach holds great promise for personalized and effective cancer treatment, paving the way for next‐generation therapeutics and diagnostics.

X-ray Attenuating Vesicles with Neutrophil Extracellular Trap (NET) Specificity: Synthesis and Testing in a Model System.

X-ray attenuating contrast agents for imaging thrombi directly during endovascular thrombectomy (EVT) are urgently needed for shortening the wait time for treatment and for reducing the chances of blood clot fragmentation. Neutrophil extracellular traps (NETs) are a product of an innate immune system response by which neutrophils release decondensed chromatin strands decorated with granule and cytosolic proteins, including neutrophil elastase and citrullinated histone H3 (CitH3). NETs are frequently found within fibrous thrombi in pathology and represent a promising target for thrombi-specific imaging agents due to their common occurrence in human cerebrovascular thrombi. We designed and tested 200 nm lipid vesicles (LV) formulated in the presence of a combination of hydrophilic and hydrophobic computed tomography (CT) contrast agents with resultant efficacy of X-ray attenuation corresponding to 312 ± 54 mg/mL iodine. The LV incorporated trans-cyclooctene-terminated pegylated distearoylphosphatidylethanolamine (TCO-PEG-DSPE) for rapid conjugation of methyltetrazine(mTz)-modified monoclonal immunoglobulin G (IgG) with anti-citH3 binding specificity. By using differential fluorescent labeling of the antibody and lipid components, we determined that 80 ± 3% of mTz-linked IgG coprecipitated with the LV after conjugation in contrast to 0.1-0.2% of control IgG. The engineered NET-specific LV were tested in vitro using differentiated human HL60 promyeloblasts (dHL60) as a standard model of NETing neutrophils. Using fibrin meshwork-incorporated dHL60 as well as monolayer cell cultures, we determined that anti-citH3 LV showed specific and high-affinity binding to dHL60 cells, which were stimulated to undergo NETosis. This work suggests the high promise of NET-specific agents in providing thrombus-specific imaging contrast during EVT.

Synthesis and Preclinical Evaluation of Novel 68Ga-DOTA-RBB as Potential PET Radiotracer for Imaging CDK4/6 in Tumors.

Many malignant tumors, including breast cancer, exhibit amplification and overexpression of cyclin-dependent kinase 4 and 6 (CDK4/6). Ribociclib, approved and used in clinical treatment, acts as a highly selective CDK4/6 inhibitor for ER+/HER2- breast cancer. By modifying ribociclib with the chelator DOTA, we designed and synthesized a novel CDK4/6-positive PET imaging agent, which was radiolabeled by 68Ga for radioactive tagging. The radiotracer demonstrates high radiochemical purity, excellent stability in vitro and in vivo, and favorable pharmacokinetic characteristics. Cell uptake experiments using MCF-7 cells indicate that an excess of ribociclib (RBB) can inhibit cellular uptake of 68Ga-DOTA-RBB. Imaging and biodistribution experiments in MCF-7 tumor-bearing nude mice show significant radioactive accumulation in the tumor. However, preadministration of excess ribociclib results in a substantial reduction in radioactive accumulation within the tumor. On the basis of our explorations, 68Ga-DOTA-RBB, as a targeted imaging agent for CDK4/6-positive tumors, holds significant potential application values.

A Phase 0 Study to Assess the Biodistribution and Pharmacokinetics of a Radiolabeled Antibody Targeting Human Kallikrein 2 in Participants with Metastatic Castration-Resistant Prostate Cancer.

Despite the inclusion of multiple agents within the prostate cancer treatment landscape, new treatment options are needed to address the unmet need for patients with metastatic castration-resistant prostate cancer (mCRPC). Although prostate-specific membrane antigen is the only cell-surface target to yield clinical benefit in men with advanced prostate cancer, additional targets may further advance targeted immune, cytotoxic, radiopharmaceutical, and other tumor-directed therapies for these patients. Human kallikrein 2 (hK2) is a novel prostate-specific target with little to no expression in nonprostate tissues. This first-in-human phase 0 trial uses an 111In-radiolabeled anti-hK2 monoclonal antibody, [111In]-DOTA-h11B6, to credential hK2 as a potential target for prostate cancer treatment. Methods: Participants with progressive mCRPC received a single infusion of 2 mg of [111In]-DOTA-h11B6 (185 MBq of 111In), with or without 8 mg of unlabeled h11B6 to assess antibody mass effects. Sequential imaging and serial blood samples were collected to determine [111In]-DOTA-h11B6 biodistribution, dosimetry, serum radioactivity, and pharmacokinetics. Safety was assessed within a 2-wk follow-up period from the time of [111In]-DOTA-h11B6 administration. Results: Twenty-two participants received [111In]-DOTA-h11B6 and are included in this analysis. Within 6-8 d of administration, [111In]-DOTA-h11B6 visibly accumulated in known mCRPC lesions, with limited uptake in other organs. Two treatment-emergent adverse events unrelated to treatment occurred, including tumor-related bleeding in 1 patient, which led to early study discontinuation. Serum clearance, biodistribution, and tumor targeting were independent of total antibody mass (2 or 10 mg). Conclusion: This first-in-human study demonstrates that tumor-associated hK2 can be identified and targeted using h11B6 as a platform as the h11B6 antibody selectively accumulated in mCRPC metastases with mass-independent clearance kinetics. These data support the feasibility of hK2 as a target for imaging and hK2-directed agents as potential therapies in patients with mCRPC.

A convolutional neural network model using intraprostatic patterns of [F18]DCFPyL uptake in PSMA PET images to predict synchronous metastases.

46 Background: [F18]DCFPyL (PyL) is a PSMA targeted imaging agent that provides whole-body staging of prostate cancer. Image analysis of the primary tumor using deep learning algorithms might offer additional insight into disease biology, including co-existing metastatic disease. We developed convolutional neural network (CNN) models using inputs from the entire prostate on PyL images along with auto-segmented hot spots within the of primary prostate cancer tumor to predict synchronous metastases and compared the models against established models built from clinico-pathologic data. Methods: 91 Veterans with de novo prostate cancer were imaged with PyL PSMA PET/CT for initial staging (46% with metastatic disease). The PyL images of the prostate were analyzed using aPROMISE, which autosegments, localizes, and quantifies disease on PSMA PET. The segmentations of the prostate were used to map the PyL PET image of the prostate. Both the entire prostate, as well as aPROMISE defined hot spots were used as inputs for the CNN, where, according to attention map analysis, the hotspot information helps the network understand the location and extent of tumors. The CNN model architecture was based on SqueezeNet v2. The dataset was split into training, validation and test sets using stratified random sampling. The area under ROC curve (AUC) was computed to determine the performance of the model in predicting the presence of metastases and the test predictions were compared with ground truth (M1). Training was repeated 50 times and the best performing experiment was identified. Prediction scores from UCSF-CAPRA and UCLA PSMA risk calculator were used as comparators. Results: The best CNN model had an AUC of 0.89 for prediction of metastatic disease (median 0.72, ICR 0.64 and 0.8). For comparison, the AUC from the UCSF-CAPRA score and UCLA-PSMA risk calculator (any upstaging on PET), which rely on clinicopathologic information, had AUCs of 0.729 and 0.754 in this dataset, respectively. Conclusions: The CNN based model using PyL imaging demonstrates that synchronous metastases can be predicted from intraprostatic PyL uptake patterns alone with a predictive accuracy in this dataset that is at least comparable to published prediction models based on clinicopathologic features. This study raises the hypothesis that PyL CNN-based models could be developed to prognosticate metastatic progression.

Synthesis and cellular uptake of neutral rhenium(I) morpholine complexes.

Morpholine motifs have been used extensively as targeting moieties for lysosomes, primarily in fluorescence imaging agents. Traditionally these imaging agents are based on organic molecules which have several shortcomings including small Stokes shifts, short emission lifetimes, and susceptibility to photobleaching. To explore alternative lysosome targeting imaging agents we have used a rhenium based phosphorescent platform which has been previously demonstrated to have an improved Stokes shift, a long lifetime emission, and is highly photostable. Rhenium complexes containing morpholine substituted ligands were designed to accumulate in acidic compartments. Two of the three complexes prepared exhibited bright emission in cells, when incubated at low concentrations (20 μM) and were non-toxic at concentrations as high as 100 μM, making them suitable for live cell imaging. We show that the rhenium complexes are amenable to chemical modification and that the morpholine targeted derivatives can be used for live cell confocal fluorescence imaging of endosomes-lysosomes.

HSA-ZW800-PEG for Enhanced Optophysical Stability and Tumor Targeting.

Small molecule fluorophores often face challenges such as short blood half-life, limited physicochemical and optical stability, and poor pharmacokinetics. To overcome these limitations, we conjugated the zwitterionic near-infrared fluorophore ZW800-PEG to human serum albumin (HSA), creating HSA-ZW800-PEG. This conjugation notably improves chemical, physical, and optical stability under physiological conditions, addressing issues commonly encountered with small molecules in biological applications. Additionally, the high molecular weight and extinction coefficient of HSA-ZW800-PEG enhances biodistribution and tumor targeting through the enhanced permeability and retention effect. The unique distribution and elimination dynamics, along with the significantly extended blood half-life of HSA-ZW800-PEG, contribute to improved tumor targetability in both subcutaneous and orthotopic xenograft tumor-bearing animal models. This modification not only influences the pharmacokinetic profile, affecting retention time and clearance patterns, but also enhances bioavailability for targeting tissues. Our study guides further development and optimization of targeted imaging agents and drug-delivery systems.

Folic acid functionalized gadolinium-doped carbon dots as fluorescence / magnetic resonance imaging contrast agent for targeted imaging of liver cancer

Gadolinium-doped carbon dots (Gd-CDs), as a new class of nanomaterial, has a wide application prospect in targeted imaging and monitoring diagnosis and treatment of liver cancer because of their good fluorescence (FL)-magnetic resonance (MR) imaging properties. First, Gd-CDs were synthesized by hydrothermal method with gadodiamide as gadolinium source, citric acid as carbon source and silane coupling agent (KH-792) as coupling agent with FL quantum yield (QY) of 48.2%. Then, folic acid (FA), which is highly expressed in liver cancer, was used as a targeting component to modify Gd-CDs to obtain targeted imaging agent (Gd-CDs-FA). The results showed that Gd-CDs and Gd-CDs-FA have low cytotoxicity and good biocompatibility, and the targeting and selectivity of Gd-CDs-FA to HepG2 cells could be observed under confocal laser scanning microscope (CLSM). The T1 longitudinal relaxation rates (r1) of Gd-CDs and Gd-CDs-FA are 15.92 mM−1s−1 and 13.56 mM−1s−1, respectively. They showed good MR imaging ability in vitro and in vivo, and MR imaging in nude mice further proved the targeting imaging performance of Gd-CDs-FA. Therefore, Gd-CDs-FA with higher QY showed good FL-MR targeting imaging ability of liver cancer, which broke through the limitations of single molecular imaging probe in sensitivity and soft tissue resolution. This study provides a new idea for the application of Gd-CDs in FL and MR targeting imaging of liver cancer.

O-54 - Preclinical evaluation of [155/161Tb]Tb-crown-TATE – a novel SPECT imaging agent targeting neuroendocrine tumors

O-54 - Preclinical evaluation of [155/161Tb]Tb-crown-TATE – a novel SPECT imaging agent targeting neuroendocrine tumors

Flotufolastat F 18: Diagnostic First Approval.

Flotufolastat F 18 (POSLUMA®) is an 18F-labelled radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted imaging agent being developed by Blue Earth Diagnostics, a subsidiary of Bracco Imaging, for prostate cancer imaging. In May 2023, flotufolastat F 18 received its first approval in the USA as a radioactive diagnostic agent for positron emission tomography (PET) of PSMA positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. This article summarizes the milestones in the development of flotufolastat F 18 leading to this first approval.

A Gold Nanocage Probe Targeting Survivin for the Diagnosis of Pancreatic Cancer.

In this paper, Au nanocages (AuNCs) loaded with the MRI contrast agent gadolinium (Gd) and capped with the tumor-targeting gene survivin (Sur-AuNC•Gd-Cy7 nanoprobes) were designed and applied as a targeted imaging agent for pancreatic cancer. With its capacity to transport fluorescent dyes and MR imaging agents, the gold cage is an outstanding platform. Furthermore, it has the potential to transport different drugs in the future, making it a unique carrier platform. The utilization of Sur-AuNC•Gd-Cy7 nanoprobes has proven to be an effective means of targeting and localizing survivin-positive BxPC-3 cells within their cytoplasm. By targeting survivin, an antiapoptotic gene, the Sur-AuNC•Gd-Cy7 nanoprobe was able to induce pro-apoptotic effects in BxPC-3 pancreatic cancer cells. The biocompatibility of AuNCs•Gd, AuNCs•Gd-Cy7 nanoparticles, and Sur-AuNC•Gd-Cy7 nanoprobes is evaluated through the hemolysis rate assay. The stability of AuNCs•Gd, AuNCs•Gd-Cy7 nanoparticles, and Sur-AuNC•Gd-Cy7 nanoprobes was evaluated by determining their hydrodynamic dimensions following storage in different pH solutions for a corresponding duration. Excellent biocompatibility and stability of the Sur-AuNC•Gd-Cy7 nanoprobes will facilitate their further utilization in vivo and in vitro. The surface-bound survivin plays a role in facilitating the Sur-AuNC•Gd-Cy7 nanoprobes' ability to locate the BxPC-3 tumor. The probe was modified to incorporate Gd and Cy7, thereby enabling the simultaneous utilization of magnetic resonance imaging (MRI) and fluorescence imaging (FI) techniques. In vivo, the Sur-AuNC•Gd-Cy7 nanoprobes were found to effectively target and localize survivin-positive BxPC-3 tumors through the use of MRI and FI. After being injected via the caudal vein, the Sur-AuNC•Gd-Cy7 nanoprobes were found to accumulate effectively in an in situ pancreatic cancer model within 24 h. Furthermore, these nanoprobes were observed to be eliminated from the body through the kidneys within 72 h after a single injection. This characteristic is crucial for a diagnostic agent. Based on the aforementioned outcomes, the Sur-AuNC•Gd-Cy7 nanoprobes have significant potential advantages for the theranostic treatment of pancreatic cancer. This nanoprobe possesses distinctive characteristics, such as advanced imaging abilities and specific drug delivery, which offer the possibility of enhancing the precision of diagnosis and efficacy of treatment for this destructive illness.

89Zr-DFO-Isatuximab for CD38-Targeted ImmunoPET Imaging of Multiple Myeloma and Lymphomas.

Multiple myeloma (MM) is the second most prevalent hematological malignancy. It remains incurable despite the availability of novel therapeutic approaches, marking an urgent need for new agents for noninvasive targeted imaging of MM lesions. CD38 has proven to be an excellent biomarker due to its high expression in aberrant lymphoid and myeloid cells relative to normal cell populations. Using isatuximab (Sanofi), the latest FDA-approved CD38-targeting antibody, we have developed Zirconium-89(89Zr)-labeled isatuximab as a novel immunoPET tracer for the in vivo delineation of MM and evaluated the extension of its applicability to lymphomas. In vitro studies validated the high binding affinity and specificity of 89Zr-DFO-isatuximab for CD38. PET imaging demonstrated the high performance of 89Zr-DFO-isatuximab as a targeted imaging agent to delineate tumor burden in disseminated models of MM and Burkitt's lymphoma. Ex vivo biodistribution studies confirmed that high accumulations of the tracer in bone marrow and bone skeleton correspond to specific disease lesions as they are reduced to background in blocking and healthy controls. This work demonstrates the promise of 89Zr-DFO-isatuximab as an immunoPET tracer for CD38-targeted imaging of MM and certain lymphomas. More importantly, its potential as an alternative to 89Zr-DFO-daratumumab holds great clinical relevance.

124I-Labeled Immuno-PET Targeting hTREM2 for the Diagnosis of Gastric Carcinoma.

Low β-2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake in gastric mucinous adenocarcinoma may cause false-negative diagnosis and erroneous staging. Thus, there is an urgent need for developing tumor-specific imaging agents in gastric cancer diagnostics. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein expressed on the surface of tumor-associated macrophages (TAMs) and is considerably overexpressed in tumor tissues. This study aimed to develop new human TREM2 (hTREM2)-targeting imaging agents to diagnose and monitor gastric cancer. We established a cell line, MGC803, with upregulated expression of hTREM2, at the cell surface. We produced a monoclonal antibody (5-mAb) against hTREM2 by immunizing mice with the hTREM2 antigen to obtain the antibody fragment 5-F(ab')2 using an immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS). Another anti-TREM2-mAb (clone 237920) and its fragment anti-TREM2-F(ab')2 were employed for the comparative study in vitro and in vivo. After 124I labeling, we constructed the probes: 124I-5-mAb, 124I-5-F(ab')2, 124I-anti-TREM2-mAb, and 124I-anti-TREM2-F(ab')2. We found that 5-mAb exhibited higher hTREM2 affinity and slower blood clearance than anti-TREM2-mAb, whose corresponding F(ab')2 fragments demonstrated the same trend. The micro-PET/CT revealed that 124I-5-F(ab')2 exhibited advantages of tumor enrichment and fast metabolism. The biodistribution study results were consistent with those of micro-PET/CT. Among the four tracers, 124I-5-F(ab')2 was the most suitable specific radiotracer for targeting hTREM2 and displayed potential utility as a tumor-imaging tracer for diagnosing gastric carcinoma.

Imaging of Indocyanine Green-Human Serum Albumin (ICG-HSA) Complex in Secreted Protein Acidic and Rich in Cysteine (SPARC)-Expressing Glioblastoma.

Glioblastoma is the most common and fatal primary glioma and has a severe prognosis. It is a challenge for neurosurgeons to remove brain tumor tissues completely by resection. Meanwhile, fluorescence-guided surgery (FGS) is a technique used in glioma surgery to enhance the visualization of tumor edges to clarify the extent of tumor resection. Indocyanine green (ICG) is the only FDA-approved NIR fluorescent agent. It non-covalently binds to human serum albumin (HSA). Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in gliomas and binds to albumin, suggesting that it plays an important role in tumor uptake of the ICG-HSA complex. Here we demonstrate the binding properties of HSA or SPARC to ICG using surface plasmon resonance and saturation binding assay. According to in vitro and in vivo studies, the results showed that the uptake of ICG-HSA complex was higher in SPARC-expressing glioblastoma cell line and tumor region compared with the uptake of free ICG. Here, we visualized the SPARC-dependent uptake of ICG and ICG-HSA complex in U87MG. Our results demonstrated that the ICG-HSA complex is likely to be used as an efficient imaging agent targeting SPARC-expressing tumors, especially glioblastoma.

Nanoparticle-based delivery systems as emerging therapy in retinoblastoma: recent advances, challenges and prospects.

Retinoblastoma is the most common intraocular malignancy in children. The treatment of this rare disease is still challenging in developing countries due to delayed diagnosis. The current therapies comprise mainly surgery, radiotherapy and chemotherapy. The adverse effects of radiation and chemotherapeutic drugs have been reported to contribute to the high mortality rate and affect patients' quality of life. The systemic side effects resulting from the distribution of chemotherapeutic drugs to non-cancerous cells are enormous and have been recognized as one of the reasons why most potent anticancer compounds fail in clinical trials. Nanoparticulate delivery systems have the potential to revolutionize cancer treatment by offering targeted delivery, enhanced penetration and retention effects, increased bioavailability, and an improved toxicity profile. Notwithstanding the plethora of evidence on the beneficial effects of nanoparticles in retinoblastoma, the clinical translation of this carrier is yet to be given the needed attention. This paper reviews the current and emerging treatment options for retinoblastoma, with emphasis on recent investigations on the use of various classes of nanoparticles in diagnosing and treating retinoblastoma. It also presents the use of ligand-conjugated and smart nanoparticles in the active targeting of anticancer and imaging agents to the tumour cells. In addition, this review discusses the prospects and challenges in translating this nanocarrier into clinical use for retinoblastoma therapy. This review may provide new insight for formulation scientists to explore in order to facilitate the development of more effective and safer medicines for children suffering from retinoblastoma.

In vivo targeting and multimodal imaging of cerebral amyloid-β aggregates using hybrid GdF3 nanoparticles.

Aim: To propose a new multimodal imaging agent targeting amyloid-β (Aβ) plaques in Alzheimer's disease. Materials & methods: A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimer's disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Results & conclusion: Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. In vivo brain uptake was dependent on the blood-brain barrier status. Nevertheless, multimodal imaging showed successful Aβ targeting in both transgenic mice and Aβ fibril-injected rats.

Macrocyclic Supramolecular Assemblies Based on Hyaluronic Acid and Their Biological Applications.

Hyaluronic acid (HA), which contains multiple carboxyl, hydroxyl, and acetylamino groups and is an agent that targets tumors, has drawn great attention in supramolecular diagnosis and treatment research. It can not only assemble directly with macrocyclic host-guest complexes through hydrogen bonding and electrostatic interactions but also can be modified with macrocyclic compounds or functional guest molecules by an amidation reaction and used for further assembly. Macrocycles play a main role in the construction of supramolecular drug carriers, targeted imaging agents, and hydrogels, such as cyclodextrins and cucurbit[n]urils, which can encapsulate photosensitizers, drugs, or other functional guest molecules via host-guest interactions. Therefore, the formed supramolecular assemblies can respond to various stimuli, such as enzymes, light, electricity, and magnetism for controlled drug delivery, enhance the luminescence intensity of the assembly, and improve drug loading capacity. In addition, the nanosupramolecular assembly formed with HA can also improve the biocompatibility of drugs, reduce drug toxicity and side effects, and enhance cell permeability; thus, the assembly has extensive application value in biomedical research. This Account mainly focuses on macrocyclic supramolecular assemblies based on HA, especially their biological applications and progress in the field, and these assemblies include (i) guest-modified HA, such as pyridinium-, adamantane-, peptide-, and other functional-group-modified HA, along with their cyclodextrin and cucurbit[n]uril assemblies; (ii) macrocycle-modified HA, such as HA modified with cyclodextrins and cucurbit[n]uril derivatives and their assembly with various guests; (iii) direct assembly between unmodified HA and cyclodextrin- or cucurbit[n]uril-based host-guest complexes. Particularly, we discussed the important role of macrocyclic host-guest complexes in HA-based supramolecular assembly, and the roles included improving the water solubility and efficacy of hydrophobic drugs, enhancing the luminescent intensity of assemblies, inducing room temperature phosphorescence and providing energy transfer systems, constructing multi-stimulus-responsive supramolecular assemblies, and in situ formation of hydrogels. Additionally, we believe that obtaining in-depth knowledge of these HA-based macrocyclic supramolecular assemblies and their biological applications encompasses many challenges regarding drug carriers, targeted imaging agents, wound healing, and biomedical soft materials and would certainly contribute to the rapid development of supramolecular diagnosis and treatment.

The Use of Medicinal Plant-Derived Metallic Nanoparticles in Theranostics.

In the quest to effectively diagnose and treat the diseases that afflict mankind, the development of a tool capable of simultaneous detection and treatment would provide a significant cornerstone for the survival and control of these diseases. Theranostics denotes a portmanteau of therapeutics and diagnostics which simultaneously detect and treat ailments. Research advances have initiated the advent of theranostics in modern medicine. Overall, theranostics are drug delivery systems with molecular or targeted imaging agents integrated into their structure. The application of theranostics is rising exponentially due to the urgent need for treatments that can be utilized for diagnostic imaging as an aid in precision and personalised medicine. Subsequently, the emergence of nanobiotechnology and the green synthesis of metallic nanoparticles (MNPs) has provided one such avenue for nanoscale development and research. Of interest is the drastic rise in the use of medicinal plants in the synthesis of MNPs which have been reported to be potentially effective in the diagnosis and treatment of diseases. At present, medicinal plant-derived MNPs have been cited to have broad pharmacological applications and have been studied for their potential use in the treatment and management of cancer, malaria, microbial and cardiovascular diseases. The subject of this article regards the role of medicinal plants in the synthesis of MNPs and the potential role of MNPs in the field of theranostics.