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We report a convenient new technique for the labeling of filamentous phage capsid proteins. Previous reports have shown that phage coat protein residues can be modified, but the lack of chemically distinct amino acids in the coat protein sequences makes it difficult to attach high levels of synthetic molecules without altering the binding capabilities of the phage. To modify the phage with polymer chains, imaging groups, and other molecules, we have developed chemistry to convert the N-terminal amines of the ~4200 coat proteins into ketone groups. These sites can then serve as chemospecific handles for the attachment of alkoxyamine groups through oxime formation. Specifically, we demonstrate the attachment of fluorophores and up to 3000 molecules of 2 kDa poly(ethylene glycol) (PEG2k) to each of the phage capsids without significantly affecting the binding of phage-displayed antibody fragments to EGFR and HER2 (two important epidermal growth factor receptors). We also demonstrate the utility of the modified phage for the characterization of breast cancer cells using multicolor fluorescence microscopy. Due to the widespread use of filamentous phage as display platforms for peptide and protein evolution, we envision that the ability to attach large numbers of synthetic functional groups to their coat proteins will be of significant value to the biological and materials communities.

We previously developed a self-referencing differential spectroscopic (SRDS) method to detect lesions by identifying a spectroscopic biomarker of breast cancer, i.e., the specific tumor component (STC). The SRDS method is based on the assumption of the exclusive presence of this spectroscopic biomaker in malignant disease. Although clinical results using this method have already been published, the dependence of the STC spectra on the choice of reference tissue has not yet been addressed. In this study, we explore the impact of the selection of the reference region size and location on the STC spectrum in 10 subjects with malignant breast tumors. Referencing from both contralateral and ipsilateral sides was performed. Regardless of the referencing, we are able to obtain consistent high contrast images of malignant lesions using the STC with less than 13% deviation. These results suggest that the STC measurements are independent of any type, location, and amount of normal breast tissue used for referencing. This confirms the initial assumption of the SRDS analysis, that there are specific tumor components in cancer that do not exist in normal tissue. This also indicates that bilateral measurements are not required for lesion identification using the STC method.

Although relatively rare in the United States, penile squamous cell carcinoma is encountered worldwide at a higher rate. Initial diagnosis is often made on clinical exam, as almost all of these lesions are externally visible and amenable to biopsy. In distinction to other types of malignancies, penile cancer relies heavily on clinical nodal staging of the inguinal lymph node chains. As with all cancers, imaging plays a role in the initial staging, restaging, and surveillance of these patients. The aim of this manuscript is to highlight the applications, advantages, and limitations of different imaging modalities in the evaluation of penile cancer, including ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography.

Purpose: Molecular imaging is one of the import methods for recognition of cancer at the early stage in order to enhance the capacity of remedy. This study was aimed to introduce a new contrast agent that was targeted with CD24 so as to improve the CT scan detection of cancer cells with higher CD24 expression. Methods: The surface modifications of gold nanoparticles (Au-NPs) were done with long PEG (HS-PEG-CH3O) and short PEG (HS-PEG-COOH) chains to enhance their stability and capacity for immobilization of different antibodies. MTT assay was carried out to assess the biocompatibility of the NPs. The obtained contrast agent was implemented in the targeted CT imaging based on in vitro and in vivo studies of breast cancer. Results: The results revealed that the attached CD24 to the cell surface of PEGylated Au-NPs could enhance significantly the cells CT number (40.45 HU in 4T1, while it was 16.61 HU in CT26) It was shown that the attenuation coefficient of the molecularly targeted cells was more than 2 times excessive than the control groups. Further, the tumor region in model of xenograft tumor has higher density compare to the omnipaque groups, 60 min after injection (45 Hu vs.81 Hu). These results showed that the nanoparticles stayed in tumor region for longer time. Conclusion: It is predicted that the synthesized nanoparticle can be used as computed tomography contrast agent. Also, it can be used to identify the tumor cells with higher expression of CD24 at the early stages more efficiently compare to the other routine methods.

Purpose: The dataset contains annotations for lung nodules collected by the Lung Imaging Data Consortium and Image Database Resource Initiative (LIDC) stored as standard DICOM objects. The annotations accompany a collection of computed tomography (CT) scans for over 1000 subjects annotated by multiple expert readers, and correspond to "nodules ≥ 3 mm", defined as any lesion considered to be a nodule with greatest in‐plane dimension in the range 3–30 mm regardless of presumed histology. The present dataset aims to simplify reuse of the data with the readily available tools, and is targeted towards researchers interested in the analysis of lung CT images. Acquisition and validation methods: Open source tools were utilized to parse the project‐specific XML representation of LIDC‐IDRI annotations and save the result as standard DICOM objects. Validation procedures focused on establishing compliance of the resulting objects with the standard, consistency of the data between the DICOM and project‐specific representation, and evaluating interoperability with the existing tools. Data format and usage notes: The dataset utilizes DICOM Segmentation objects for storing annotations of the lung nodules, and DICOM Structured Reporting objects for communicating qualitative evaluations (nine attributes) and quantitative measurements (three attributes) associated with the nodules. The total of 875 subjects contain 6859 nodule annotations. Clustering of the neighboring annotations resulted in 2651 distinct nodules. The data are available in TCIA at https://doi.org/10.7937/TCIA.2018.h7umfurq. Potential applications: The standardized dataset maintains the content of the original contribution of the LIDC‐IDRI consortium, and should be helpful in developing automated tools for characterization of lung lesions and image phenotyping. In addition to those properties, the representation of the present dataset makes it more FAIR (Findable, Accessible, Interoperable, Reusable) for the research community, and enables its integration with other standardized data collections. [ABSTRACT FROM AUTHOR]

Submicron phase-change droplets are an emerging class of ultrasound contrast agent. Compared with microbubbles, their relatively small size and increased stability offer the potential to passively extravasate and accumulate in solid tumors through the enhanced permeability and retention effect. Under exposure to sufficiently powerful ultrasound, these droplets can convert into in situ gas microbubbles and thus be used as an extravascular-specific contrast agent. However, in vivo imaging methods to detect extravasated droplets have yet to be established. Here, we develop an ultrasound imaging pulse sequence within diagnostic safety limits to selectively detect droplet extravasation in tumors. Tumor-bearing mice were injected with submicron perfluorobutane droplets and interrogated with our imaging-vaporization-imaging sequence. By use of a pulse subtraction method, median droplet extravasation signal relative to the total signal within the tumor was estimated to be Etumor=37±5% compared with the kidney Ekidney=-2±8% (p < 0.001). This work contributes toward the advancement of volatile phase-shift droplets as a next-generation ultrasound agent for imaging and therapy. [ABSTRACT FROM AUTHOR]

Purpose: The potential of L‐glutamine as a T2 exchange contrast agent in MRI was investigated. Methods: The T2 relaxation rate of L‐glutamine solutions prepared in various concentrations was measured at 9.4 T. A series of T2‐weighted images in a mouse cancer model was acquired with an L‐glutamine solution infusion. Results: The T2 relaxivity caused by the exchange (R2ex) at 37°C was 0.069 s−1 mM−1 and 0.102 s−1 mM−1 for glutamine and glutamate solutions at pH = 7.2, respectively. The R2ex of glutamine at pH = 6.1–6.7 was in the 0.097–0.1 s−1 mM−1 range. No significant dependence of T1 on the concentration of glutamine was observed. The dynamic measurement of T2‐weighted images in vivo showed that the glutamine uptake was primarily observed at the localized part of the tumor Conclusion: L‐glutamine can be used as a T2 exchange contrast agent and images of glutamine uptake in vivo can be acquired. [ABSTRACT FROM AUTHOR]

In the battle against cancer, timely diagnosis is critical for successful treatment. The major limitation in detecting cancer at early development stages is the unavailability of sensitive and specific detection methods. Nanobiology combines biology with physics and chemistry to generate several new areas such as nanodiagnostics and nanotheranostics. Nanodiagnostics involve the development of new strategies and innovations to enhance the current detection methods in tumor biology. Another important aspect of nanodiagnostics is to improve personalized cancer detection and real-time monitoring of treatments assisted by imaging modalities. Nanotheranostics combines therapy and diagnosis in a single model for cancer detection and treatment thus providing the advantage of targeted drug delivery and fewer side effects to normal tissues. In this review, we have outlined diverse nanoparticle systems for early cancer detection and therapy. A wide variety of nanomaterial-based approaches such as nanobubbles, quantum dots, liposomes, or nanotubes demonstrate huge potential in improving imaging methods to screen and monitor cancer progression. Although a significant amount of contributions have been directed to develop nanodiagnostics systems, they are still at preclinical stage. Thus, it is a dynamic area for research with encouraging development towards the clinical stage. [ABSTRACT FROM AUTHOR]

Background: Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment. Methods: In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour. Results: Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg−1 and 0.3 mg kg−1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly. Conclusions: Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging. [ABSTRACT FROM AUTHOR]

L‐2‐[18F]fluoro‐alpha‐methylphenylalanine (2‐[18F]FAMP) is a promising amino acid tracer for positron emission tomography (PET) imaging, yet the low production yield of direct electrophilic radiofluorination with [18F]F2 necessitates further optimization of the radiolabeling process. This paper describes a two‐step preparation method for L‐2‐[18F]fluoro‐alpha‐methylphenylalanine (2‐[18F]FAMP) starting from [18F]fluoride. The (Mesityl)(L‐alpha‐methylphenylalanine)‐2‐iodonium tetrafluoroborate precursors with various protecting groups were prepared. The copper‐mediated 18F‐fluorination of the iodonium salt precursors successfully produced 2‐[18F]FAMP. The highest radio chemical conversion of 57.6% was noted with N‐Piv‐protected (mesityl)(aryl)iodonium salt in the presence of 5 equivalent of Cu (OTf)2. Subsequent deprotection with 57% hydrogen iodide produced 2‐[18F]FAMP within 120 min in 21.4 ± 11.7% overall radiochemical yield with >95% radiochemical purity and an enantiomeric excess >99%. The obtained 2‐[18F]FAMP showed comparable biodistribution profiles in normal mice with that of the carrier‐added 2‐[18F]FAMP. These results indicate that usefulness of copper mediated 18F‐fluorination for the production of 2‐[18F]FAMP, which would facilitate clinical translation of the promising tumor specific amino acid tracer. Individual facilities could adopt either production method based on radioactivity demand and equipment availability. [ABSTRACT FROM AUTHOR]

Nanoparticles are excellent imaging agents for cancer, but variability in chemical structure, racemic mixtures, and addition of heavy metals hinders FDA approval in the United States. We developed a sm all u ltra- r ed f luorescent p rotein, named smURFP, to have optical properties similar to the small-molecule Cy5, a heptamethine subclass of cyanine dyes (Ex/Em = 642/670 nm). smURFP has a fluorescence quantum yield of 18% and expresses so well in E. coli , that gram quantities of fluorescent protein are purified from cultures in the laboratory. In this research, the fluorescent protein smURFP was combined with bovine serum albumin into fluorescent protein nanoparticles. These nanoparticles are fluorescent with a quantum yield of 17% and 12–14 nm in diameter. The far-red fluorescent protein nanoparticles noninvasively image tumors in living mice via the enhanced permeation and retention (EPR) mechanism. This manuscript describes the use of a new fluorescent protein nanoparticle for in vivo fluorescent imaging. This protein nanoparticle core should prove useful as a biomacromolecular scaffold, which could bear extended chemical modifications for studies, such as the in vivo imaging of fluorescent protein nanoparticles targeted to primary and metastatic cancer, theranostic treatment, and/or dual-modality imaging with positron emission tomography for entire human imaging. [ABSTRACT FROM AUTHOR]

Purpose: Tumor response assessments on positron emission tomography (PET)/magnetic resonance imaging (MRI) scans require correct quantification of radiotracer uptake in tumors and normal organs. Historically, MRI scans have been enhanced with gadolinium (Gd)-based contrast agents, which are now controversial due to brain deposition. Recently, ferumoxytol nanoparticles have been identified as an alternative to Gd-based contrast agents because they provide strong tissue enhancement on MR images but are not deposited in the brain. However, it is not known if the strong T1- and T2-contrast obtained with iron oxide nanoparticles such as ferumoxytol could affect MR-based attenuation correction of PET data. The purpose of our study was to investigate if ferumoxytol administration prior to a 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG PET/MR scan would change standardized uptake values (SUV) of normal organs.Procedures: Thirty pediatric patients (6-18 years) with malignant tumors underwent [18F]FDG-PET/MR scans (dose 3 MBq/kg). Fifteen patients received an intravenous ferumoxytol injection (5 mg Fe/kg) prior to the [18F]FDG-PET/MR scans (group 1). Fifteen additional age- and sex-matched patients received unenhanced [18F]FDG-PET/MR scans (group 2). For attenuation correction of PET data, we used a Dixon-based gradient echo sequence (TR 4.2 ms, TE 1.1, 2.3 ms, FA 5), which accounted for soft tissue, lung, fat, and background air. We used a mixed linear effects model to compare the tissue MRI enhancement, quantified as the signal-to-noise ratio (SNR), as well as tissue radiotracer signal, quantified as SUVmean and SUVmax, between group 1 and group 2. Alpha was assumed at 0.05.Results: The MRI enhancement of the blood and solid extra-cerebral organs, quantified as SNR, was significantly higher on ferumoxytol-enhanced MRI scans compared to unenhanced scans (p < 0.001). However, SUVmean and SUVmax values, corrected based on the patients' body weight or body surface area, were not significantly different between the two groups (p > 0.05).Conclusion: Ferumoxytol administration prior to a [18F]FDG PET/MR scan did not change standardized uptake values (SUV) of solid extra-cerebral organs. This is important, because it allows injection of ferumoxytol contrast prior to a PET/MRI procedure and, thereby, significantly accelerates image acquisition times. [ABSTRACT FROM AUTHOR]

This work is motivated by multimodality breast cancer imaging data, which is quite challenging in that the signals of discrete tumor-associated microvesicles are randomly distributed with heterogeneous patterns. This imposes a significant challenge for conventional imaging regression and dimension reduction models assuming a homogeneous feature structure. We develop an innovative multilayer tensor learning method to incorporate heterogeneity to a higher-order tensor decomposition and predict disease status effectively through utilizing subject-wise imaging features and multimodality information. Specifically, we construct a multilayer decomposition which leverages an individualized imaging layer in addition to a modality-specific tensor structure. One major advantage of our approach is that we are able to efficiently capture the heterogeneous spatial features of signals that are not characterized by a population structure as well as integrating multimodality information simultaneously. To achieve scalable computing, we develop a new bi-level block improvement algorithm. In theory, we investigate both the algorithm convergence property, tensor signal recovery error bound and asymptotic consistency for prediction model estimation. We also apply the proposed method for simulated and human breast cancer imaging data. Numerical results demonstrate that the proposed method outperforms other existing competing methods. for this article are available online. [ABSTRACT FROM AUTHOR]

Ultra Quenchbody (UQ‐body) is a biosensor that utilizes the quenching behavior of the fluorescent dye linked to the antibody V region. When the corresponding antigen is bound to the UQ‐body, the fluorescence is restored and allows the detection of target molecules easily and sensitively. In this paper, we constructed UQ‐bodies to sensitively detect the human epidermal growth factor receptor 2 (HER2) cancer marker in solution or on cancer cells, which was further used to kill the cancer cells. A synthetic Fab fragment of anti‐HER2 antibody Fab37 with many Trp residues at hypervariable region was prepared and labeled with fluorescent dyes to obtain the UQ‐bodies. The UQ‐body could detect HER2 in solution at concentrations as low as 20 pM with an EC50 of 0.3 nM with a fourfold response. Fluorescence imaging of HER2‐positive cells was successfully performed without any washing steps. To deliver small interfering RNA (siRNA) to cancer cells, a modified UQ‐body with C‐terminal 9R sequence was also prepared. HER2‐positive cancer cells were effectively killed by polo‐like kinase 1 siRNA intracellularly delivered by the UQ‐body‐9R. The novel approach employing siRNA‐empowered UQ‐body could detect and image the HER2 antigen easily and sensitively, and effectively kill the HER2‐positive cancer cells. [ABSTRACT FROM AUTHOR]

Objective: Vascular permeability (VP) is a mechanical parameter which plays an important role in cancer initiation, metastasis, and progression. To date, there are only a few non-invasive methods that can be used to image VP in solid tumors. Most of these methods require the use of contrast agents and are expensive, limiting widespread use. Methods: In this paper, we propose a new method to image VP in tumors, which is based on the use of ultrasound poroelastography. Estimation of VP by poroelastography requires knowledge of the Young's modulus (YM), Poisson's ratio (PR), and strain time constant (TC) in the tumors. In our method, we find the ellipse which best fits the tumor (regardless of its shape) using an eigen-system-based fitting technique and estimate the YM and PR using Eshelby's elliptic inclusion formulation. A Fourier method is used to estimate the axial strain TC, which does not require any initial guess and is highly robust to noise. Results: It is demonstrated that the proposed method can estimate VP in irregularly shaped tumors with an accuracy of above $\text{80}\%$ using ultrasound simulation data with signal-to-noise ratio of 20 dB or higher. In vivo feasibility of the proposed technique is demonstrated in an orthotopic mouse model of breast cancer. Conclusion: The proposed imaging method can provide accurate and localized estimation of VP in cancers non-invasively and cost-effectively. Significance: Accurate and non-invasive assessment of VP can have a significant impact on diagnosis, prognosis, and treatment of cancers. [ABSTRACT FROM AUTHOR]

Survivin belongs to the inhibitor of apoptosis protein family, which is consistently overexpressed in most cancer cells but rarely expressed in normal adult tissues. Therefore, the detection and inhibition of survivin are regarded as attractive strategies for cancer‐specific treatment. In this study, we designed and synthesized 7‐19 residues of inner centromere protein (INCENP)‐derived small peptides (INC peptides) as novel survivin‐targeting agents. The INC peptides showed binding affinity for the human survivin protein (Kd = 91.4‐255 nmol L−1); INC16‐22, which contains residues 16‐22 of INCENP, showed the highest affinity (91.4 nmol L−1). Confocal fluorescence imaging showed consistent colocalization of FITC‐INC16‐22 and survivin in cell lines. Nona‐arginine‐linked INC16‐22 (r9‐INC16‐22) rendered INC16‐22 cells penetrable and strongly inhibited cell growth of MIA PaCa‐2 cells (52% inhibition at 1.0 µmol L−1) and MDA‐MB‐231 cells (60% inhibition at 10 µmol L−1) as determined by MTT assays. The exposure of MIA PaCa‐2 cells to 40 µmol L−1 r9‐INC16‐22 apparently reduced the intracellular protein expression levels of survivin. However, cleaved caspase‐3 was significantly increased in cells treated with r9‐INC16‐22, even at 10 µmol L−1, compared to untreated cells. Flow cytometry revealed that r9‐INC16‐22 strongly induced apoptosis in MIA PaCa‐2 cells. These results indicate that the cytotoxic effects of r9‐INC16‐22 could be mediated mainly through the disruption of survivin‐dependent antiapoptotic functions and partly because of the direct degradation of the survivin protein. Our findings suggest that INC peptides can act as useful scaffolds for novel cancer imaging and anticancer agents. [ABSTRACT FROM AUTHOR]

Multi-modality imaging agents are desirable for tumor diagnosis because they can provide more alternative and reliable information for accurate detection and therapy of diseases than single imaging technique. However, most reported conventional imaging agents have not been found to successfully overcome the disadvantages of traditional diagnoses such as sensitivity, spatial resolution, short half-decay time and complexity. Therefore, exploring a multifunctional nanocomposite with the combination of their individual modality characteristics has great impact on preoperative imaging and intraoperative diagnosis of cancer. In our study, mesoporous silica gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) specifically for preoperative and intraoperative imaging are designed and their imaging capability and biosafety are examined. They exhibit strong attenuation property for computed X-ray tomography (CT) imaging, high T 1 relaxivity for magnetic resonance (MR) imaging capability and surface-enhanced Raman spectroscopy (SERS) signal with good dispersity and stability, which presents CT/MR/SERS multi-mode imaging performance of the tumor of mice within a given time. Furthermore, in vivo biodistribution and long-term toxicity studies reveal that the Gd-GERTs have good biocompatibility and bio-safety. Therefore, Gd-GERTs are of great potential as a multifunctional nanoplatform for accurate preoperative CT/MRI diagnosis and intraoperative Raman imaging-guide resection of cancers. Recent advances in molecular imaging technology have provided a myriad of opportunities to prepare various nanomaterials for accurate diagnosis and response evaluation of cancer via different imaging modalities. However, single bioimaging modality is still challenging to overcome the issues such as sensitivity, spatial resolution, imaging speed and complexity for clinicians. In this work, we designed a kind of unique multifunctional nanoprobes with computed X-ray tomography/magnetic resonance/surface-enhanced Raman spectroscopy (CT/MR/SERS) triple-modal imaging capabilities. Multifunctional nanotags offer the capabilities of preoperative noninvasive CT/MR imaging for identification of tumors as well as intraoperative real-time SERS imaging for guidance of complete resection of tumors. These multifunctional nanoprobes show critical clinical significance on the improvement of tumor diagnosis and therapy. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The Neck Imaging Reporting and Data System (NI‐RADS) was conceived in 2016 with the objective of standardizing assessment and reporting in surveillance imaging for patients with head and neck squamous cell carcinomas and their subsequent management. The goals are to simplify radiology reports while increasing the consistency and accuracy of the interpretation of cancer surveillance imaging; enable better communication among clinicians and between clinicians and patients; facilitate outcomes research; and ultimately improve patient survival, morbidity, and mortality. The objective of the current study was to provide the background as to why and how NI‐RADS was conceived and what it entails in radiology reporting. Neck Imaging Reporting and Data System (NI‐RADS) was conceived in 2016 with the objective of standardizing assessment and reporting in surveillance imaging for patients with head and neck squamous cell carcinomas and their subsequent management. This commentary aims to provide the background regarding why and how NI‐RADS was conceived and what it entails in radiology reporting. [ABSTRACT FROM AUTHOR]

Purpose: Oncologic imaging in the emergency department (ED) is frequently encountered, including non-acute scans known as "metastatic workups" or "staging" (referred to as "cancer staging computed tomography (CT) exams"). This study examines the impact of oncologic staging CT exams on ED imaging turnaround time (TAT), defined as the time from the end of the CT exam to a final signed radiologist report, as well as order to scan completion time.Methods: A retrospective review was conducted of all adult patients presenting to an urban, quaternary academic medical center ED from February 2016 to September 2017, who had CT imaging ordered, performed, and interpreted in the ED imaging department. CT exams containing institution-specific cancer descriptors were included. After excluding all acute exams, cancer staging CT exams were compared to a matched cohort of non-oncologic ED CT exams to evaluate median TAT and order to scan completion time using a log transformed multivariable linear regression.Results: Adjusting for age and CT body part, cancer staging CT exams were associated with an independently statistically significant increased median log TAT compared to non-oncologic ED CT exams (114.5 min [IQR 112] versus 69 min [IQR 67], respectively, p < .0001) and an independently statistically significant increased median log initial order to scan completion time (166 min [IQR: 89] vs 119 min [IQR: 93], p < .0001).Conclusion: Oncology patients receiving non-acute metastatic workup scans in the ED have a significantly longer TAT compared to non-oncologic ED CT exams as well as longer order to scan completion times. [ABSTRACT FROM AUTHOR]

Cancer cells reprogram their gene expression to promote growth, survival, proliferation, and invasiveness. The unique expression of certain uptake transporters in cancers and their innate function to concentrate small molecular substrates in cells make them ideal targets for selective delivering imaging and therapeutic agents into cancer cells. In this review, we focus on several solute carrier (SLC) transporters known to be involved in transporting clinically used radiopharmaceutical agents into cancer cells, including the sodium/iodine symporter (NIS), norepinephrine transporter (NET), glucose transporter 1 (GLUT1), and monocarboxylate transporters (MCTs). The molecular and functional characteristics of these transporters are reviewed with special emphasis on their specific expressions in cancers and interaction with imaging or theranostic agents [ e.g., I-123, I-131, 123I-iobenguane (mIBG), 18F-fluorodeoxyglucose (18F-FDG) and 13C pyruvate]. Current clinical applications and research areas of these transporters in cancer diagnosis and treatment are discussed. Finally, we offer our views on emerging opportunities and challenges in targeting transporters for cancer imaging and treatment. By analyzing the few clinically successful examples, we hope much interest can be garnered in cancer research towards uptake transporters and their potential applications in cancer diagnosis and treatment. Certain uptake transporters are highly expressed in cancer cells, making them ideal targets for selectively delivering imaging and therapeutic agents into tumor cells. For instance, 123I-mIBG used in neuroblastoma imaging is concentrated into tumor lesions (arrows) by the norepinephrine transporter. Tumor lesions are not observed after treatment. (The 123I-mIBG scan image was originally published by Pandit-Taskar and Modak, J Nucl Med 2017;58:39S-53S. SNMMI©). Image 1 [ABSTRACT FROM AUTHOR]

Purpose: Fluorine-18 labeled tryptophan analog L-1-[18F]fluoroethyl-tryptophan (L-1-[18F]FETrp) was designed for positron emission tomography (PET) imaging of cancer by dual targeting of the overexpressed amino acid transporters and altered indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway of tryptophan metabolism. In our previous study, we described the radiosynthesis and preliminary evaluation of L-1-[18F]FETrp for PET imaging of breast cancer. The aim of this study was to investigate the in vivo imaging mechanism and further evaluate this radiotracer in more wide range types of cancers including prostate cancer, lung cancer, and glioma.Procedures: The mice bearing subcutaneous PC-3 prostate cancer, subcutaneous H2009 and H460 lung cancers, subcutaneous MDA-MB-231, orthotopic A549 lung cancer, and intracranial 73C glioma were employed to evaluate L-1-[18F]FETrp for PET imaging of cancer. The in vivo catabolism of L-1-[18F]FETrp in the tumor was studied by analysis of PC-3 extracts with radio-HPLC.Results: Small animal PET/CT imaging of L-1-[18F]FETrp visualized all tumors in these different mouse models with high accumulations of radioactivity in PC-3 (7.5 ± 0.6 % ID/g), H2009 (5.3 ± 0.8 % ID/g), H460 (9.0 ± 1.4 % ID/g), A549 (4.5 ± 0.5 % ID/g), and 73C (4.1 ± 0.7 % ID/g) tumors. The radio-HPLC analysis of PC-3 tumor extracts revealed that about 30 % of L-1-[18F]FETrp was converted into a highly polar radioactive metabolite. The uptake in H460 cancer was about 1.7-fold higher than that in H2009 cancer, which indicated L-1-[18F]FETrp could differentiate these subtypes of lung cancers (H2009 and H460) by imaging quantification. Furthermore, small animal PET/CT imaging in intracranial glioma revealed L-1-[18F]FETrp could pass blood-brain barrier (BBB) and accumulate in glioma with a favorable imaging contrast (tumor-to-brain 2.9).Conclusions: L-1-[18F]FETrp highly accumulated in a wide range of malignancies including lung cancer, prostate cancer, and glioma. These results suggested that L-1-[18F]FETrp is a promising radiotracer for PET imaging of cancer. [ABSTRACT FROM AUTHOR]

Utility of glycol-chitosan-coated gold nanoparticles (GC-AuNPs) as a photoacoustic contrast agent for cancer cell imaging was demonstrated. Through the synergistic effect of glycol chitosan and gold nanoparticles, GC-AuNPs showed cellular uptake in breast cancer cells and resulted in strong photoacoustic signals in tissue-mimicking cell phantoms. The performance of GC-AuNPs as contrast agents was established with photoacoustic imaging and confirmed with dark-field microscopy. The cell phantoms displayed strong photoacoustic signals if cells were incubated more than 3 h with GC-AuNPs, compared with PEG-AuNPs that showed no photoacoustic signal increase. The enhanced photoacoustic signals originated from the plasmon coupling effect of GC-AuNPs after the cellular uptake in cancer cells. Importantly, photoacoustic imaging of cancer cells was achieved with GC-AuNPs--contrast agents that did not require antibodies or complex surface modification. The endocytosis of GC-AuNPs was also confirmed with dark-field microscopy. The results show that GC-AuNPs have potential as a photoacoustic contrast agent for cellular imaging including tumor tissue imaging. [ABSTRACT FROM AUTHOR]

With the arrival of the precision medicine and personalized treatment era, targeted therapy that improves efficacy and reduces side effects has become the mainstream approach of cancer treatment. Antibody fragments that further enhance penetration and retain the most critical antigen-specific binding functions are considered the focus of research targeting cancer imaging and therapy. Thanks to the superior penetration and rapid blood clearance of antibody fragments, antibody fragment-based imaging agents enable efficient and sensitive imaging of tumour sites. In tumour-targeted therapy, antibody fragments can directly inhibit tumour proliferation and growth, serve as an ideal carrier for delivery of anti-tumour drugs, or manipulate the immune system to eliminate tumour cells. In this review, the excellent physicochemical properties and the basic structure of antibody fragments are expressly depicted depicted, the progress of antibody fragments in cancer therapy and imaging are thoroughly summarized, and the future development of antibody fragments is predicted. [ABSTRACT FROM AUTHOR]

The multifunctional NaYF 4 :Yb,Er@SiO 2 @Fe 3 O 4 with upconversion luminescence and superparamagnetic properties were obtained for imaging and phototherapy in the optical biological windows. [Display omitted] • The multifunctional nanoparticles with upconversion luminescence and superparamagnetic properties were synthesized. • The heat generation ability of the nanoparticles upon their irradiation with 808 nm and 880 nm laser light was obtained. • The multifunctional nanoconstruct suitable for imaging and phototherapy in the optical biological windows was obtained. Multifunctional opto-magnetic nanoparticles (NPs) with upconverting properties were designed for cancer detection and treatment. The upconversion was achieved from NaYF 4 doped by 20 %Yb and 2 % Er nanoparticles (UCNPs). The UCNPs were coated by a thin SiO 2 shell and decorated with 6 nm magnetic Fe 3 O 4 that resulted in the formation of NaYF 4 :Yb,Er@SiO 2 @Fe 3 O 4 multifunctional nanoplatform. The connection between UCNPs and Fe 3 O 4 NPs was proved by SEM, TEM, SQUID, absorption, and luminescence techniques. The specific absorption rate (SAR) values for prepared colloids were calculated for colloidal suspension of heterostructures after 808 and 880 nm laser irradiation as a function of lasers power. The highest conversion effectiveness was obtained for an 880 nm light source with 1600 mW (SAR = 87 W/g). The low MDA-MB-231 cells cytotoxicity of NaYF 4 :Yb,Er@SiO 2 @Fe 3 O 4 NPs was observed (up to 500 µg/ml). At the same time, a strong upconverting signal after 980 nm of excitation was observed from the sites of the cells without autofluorescence from its components. This phenomenon with relatively good SAR parameters suggested that multifunctional nanoconstructs for simultaneous cancer detection (imaging) and photothermal therapy have been successfully obtained. [ABSTRACT FROM AUTHOR]

Cancer patients face a significant clinical and socio-economic burden due to increased incidence, mortality, and poor survival. Factors like late diagnosis, recurrence, drug resistance, severe side effects, and poor bioavailability limit the scope of current therapies. There is a need for novel, cost-effective, and safe diagnostic methods, therapeutics to overcome recurrence and drug resistance, and drug delivery vehicles with enhanced bioavailability and less off-site toxicity. Advanced nanomaterial-based research is aiding cancer biologists by providing solutions for issues like hypoxia, tumor microenvironment, low stability, poor penetration, target non-specificity, and rapid drug clearance. Currently, nanozymes and carbon-dots are attractive due to their low cost, high catalytic activity, biocompatibility, and lower toxicity. Nanozymes and carbon-dots are increasingly used in imaging, biosensing, diagnosis, and targeted cancer therapy. Integrating these materials with advanced diagnostic tools like CT scans and MRIs can aid in clinical decision-making and enhance the effectiveness of chemotherapy, photothermal, photodynamic, and sonodynamic therapies, with minimal invasion and reduced collateral effects. [Display omitted] [ABSTRACT FROM AUTHOR]