Imaging Contrast Research Articles

Multifunctional Dendrimer-Peptide Conjugates for MET Receptor-specific Imaging of Cancer Cells

The Mesenchymal Epithelial Transition (MET) receptor tyrosine kinase is frequently upregulated or mutated in various cancers. Targeting MET signaling pathway has been utilized as a treatment for cancer, as since MET overexpression is often associated with poor prognosis. Selective imaging of MET-overexpressing tumor cells would thus provide a high diagnostic value; however, it remains elusive due to a lack of targeted imaging contrast agents. Herein, we have developed a multifunctional diagnostic dendrimer-peptide conjugate (DPC) system with a strong avidity to MET-expressing cancer cells. The system was prepared by conjugating MET-inhibiting peptides (C7) to generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers. Due to the dendrimer-mediated multivalent binding effect, the DPCs exhibited a significantly stronger binding to the human MET protein than free C7, as measured using surface plasmon resonance. Confocal microscopy revealed increased binding of the DPCs to the MET-expressing EBC-1 and UW-Lung-21 cells, whereas a MET knock-out cell line showed negligible interactions with the DPCs. The DPCs were then conjugated with Zirconium-89 for positron emission tomography and computed tomography (PET/CT) scanning, demonstrating their selective accumulation to MET-expressing tumors in vivo. Additionally, the plasma half-life of the DPCs was measured at ~53hours, which was significantly longer than free C7. These results collectively suggest that this DPC system has potential as a targeted imaging platform specific to MET-expressing tumors, which would be applicable to various cancer types.

Confounded Magnetic Resonance Imaging Contrast Agent Exposures and Gadolinium Retention in Organs

Confounded Magnetic Resonance Imaging Contrast Agent Exposures and Gadolinium Retention in Organs

Relaxivity Modulation of Gd-HPDO3A-like Complexes by Introducing Polar and Protic Peripheral Groups

In the last three decades, high-relaxivity Magnetic Resonance Imaging (MRI) contrast agents (CAs) have been intensively sought, aiming at a reduction in the clinically injected dose while maintaining the safety of the CA and obtaining the same pathological information. Thus, four new Gd(III) complexes based on modified 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) macrocyclic structure were designed and synthesized by introducing further polar and protic functional groups (amides, phosphonates, and diols) adjacent to the metal-coordinated hydroxyl group. A detailed 1H NMR relaxometric analysis allowed us to investigate the effect of these functional groups on the relaxivity, which showed a 20–60% increase (at 0.5 T, 298 K, and pH 7.4) with respect to that of clinically approved CAs. The contribution of the water molecules H-bonded to these peripheral functional groups on the relaxivity was evaluated in terms of the second sphere effect or prototropic exchange of labile protons.

Density and Time Characteristics of CSF-venous fistulas on CT myelography in Patients with Spontaneous Intracranial Hypotension.

The conspicuity of CSF-venous fistulas (CVF) on specialized myelographic imaging protocols varies, and the factors that determine their visibility have not yet been extensively studied. The purpose of this study was to determine the relative effect of two variables on CVF visibility: timing of imaging and intrathecal contrast density. Retrospective cohort of 24 patients with spontaneous intracranial hypotension due to a CVF who underwent a total of 34 CT myelographies. All CTM acquisitions that included the level of the known definite CVF were evaluated for (1) time passed after injection of contrast, (2) attenuation of the adjacent subarachnoid space, (3) subjective visibility of the CVF on that series,(4) attenuation of the corresponding draining vein and (5) contrast dose used. A total of 131 acquisitions included the level of the known CVFs. Attenuation values of the thecal sac were significantly higher in acquisitions where the CVFs were definitely visible (average 2283 HU) than on acquisitions where the CVFs were equivocal or not visible (764 HU and 583 HU respectively). No significant difference was shown in the timing of the acquisitions between the three groups (12.8 min, 20.4 min and 17.5 min respectively). Multivariate linear regression showed thecal sac density to be the only independent predictor of the density of the CVF draining vein, while time passed after contrast injection was not independently correlated. Intrathecal contrast density has a strong positive relationship with the visibility of CVF. Timing of the acquisition was not an independent predictor of CVF visibility under our acquisition protocolABBREVIATIONS: LDCTM = lateral decubitus CT myelography; CVF = CSF-venous fistula; IOCM = iodinated contrast media.

Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY).

Smart radiotherapy biomaterials (SRBs) include seed and liquid biomaterials designed to be employed as fiducial markers during radiotherapy while also delivering therapeutic drug payloads to enhance treatment outcomes. In this study, we investigate a novel Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY) biomaterial, which can be loaded with immunoadjuvants (anti-CD40 monoclonal antibody or Caflanone (FBL-03G)) at the point of care. The CLARITY biomaterial was investigated in an animal model of pancreatic cancer using C57BL6 mice. Mice were imaged before and at different points of time post-treatment to evaluate the potential of CLARITY biomaterial to provide imaging contrast similar to fiducials. This study also used cadavers to assess CLARITY's potential to provide imaging contrast in humans. Results showed imaging contrast from computed tomography (CT) and magnetic resonance imaging (MRI) modalities for up to 30 days post-treatment, demonstrating potential for use as fiducials. A significant increase in survival (***, p = 0.0006) was observed for mice treated with CLARITY biomaterial loaded with immunoadjuvant for up to 10 weeks post-treatment compared to those without treatment. These initial results demonstrate the potential of CLARITY biomaterial to serve as a smart multifunctional radiotherapy biomaterial and provide the impetus for further development and optimization as a point-of-care technology for combination radiotherapy and immunotherapy.

Prospective longitudinal analysis of imaging-based spatiotemporal tumor habitats in glioblastoma, IDH-wild type: implication in patient outcome using multiparametric physiologic MRI

BackgroundPhysiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT).MethodsIn this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats.DiscussionThe perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma.Trial registrationClinicalTrials.gov ID: NCT02613988.

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.

Characterisation of Gas Vesicles as Cavitation Nuclei for Ultrasound Therapy using Passive Acoustic Mapping.

Genetically encodable gas filled particles known as gas vesicles (GVs) have shown promise as a biomolecular contrast agent for ultrasound imaging and have the potential to be used as cavitation nuclei for ultrasound therapy. In this study, we used passive acoustic mapping techniques to characterize GV-seeded cavitation, utilizing 0.5 and 1.6 MHz ultrasound over peak rarefactional pressures ranging from 100 to 2200 kPa. We found that GVs produce cavitation for the duration of the first applied pulse, up to at least 5000 cycles, but that bubble activity diminishes rapidly over subsequent pulses. At 0.5 MHz the frequency content of cavitation emissions was predominantly broadband in nature, whilst at 1.6 MHz narrowband content at harmonics of the main excitation frequency dominated. Simulations and high-speed camera imaging suggest that the received cavitation emissions come not from individual GVs but instead from the coalescence of GV-released gas into larger bubbles during the applied ultrasound pulse. These results will aid the future development of GVs as cavitation nuclei in ultrasound therapy.

Contrast and quantum noise in single-exposure dual-energy thoracic imaging with photon-counting x-ray detectors

Objective.Photon-counting x-ray detectors (PCDs) can produce dual-energy (DE) x-ray images of lung cancer in a single x-ray exposure. It is important to understand the factors that affect contrast, noise and the contrast-to-noise ratio (CNR). This study quantifies the dependence of CNR on tube voltage, energy threshold and patient thickness in single exposure, DE, bone-suppressed thoracic imaging with PCDs, and elucidates how the fundamental processes inherent in x-ray detection by PCDs contribute to CNR degradation.Approach.We modeled the DE CNR for five theoretical PCDs, ranging from an ideal PCD that detects every primary photon in the correct energy bin while rejecting all scattered radiation to a non-ideal PCD that suffers from charge-sharing and electronic noise, and detects scatter. CNR was computed as a function of tube voltage and high energy threshold for average and larger-than-average patients. Model predictions were compared with experimental data extracted from images acquired using a cadmium telluride (CdTe) PCD with two energy bins and analog charge summing for charge-sharing suppression. The imaging phantom simulated attenuation, scatter and contrast in lung nodule imaging. We quantified CNR improvements achievable with anti-correlated noise reduction (ACNR) and measured the range of exposure rates over which pulse pile-up is negligible.Main Results.The realistic model predicted overall trends observed in the experimental data. CNR improvements with ACNR were approximately five-fold, and modeled CNR-enhancements were on average within 10% of experiment. CNR increased modestly (i.e.<20%) when increasing the tube voltage from 90 kV to 130 kV. Optimal energy thresholds ranged from 50 keV to 70 keV across all tube voltages and patient thicknesses with and without ACNR. Quantum efficiency, electronic noise, charge sharing and scatter degraded CNR by ~50%. Charge sharing and scatter had the largest effect on CNR, degrading it by ~30% and ~15% respectively. Dead-time losses were less than 5% for patient exposure rates within the range of clinical exposure rates.Significance.In this study, we (1) employed analytical and computational models to assess the impact of different factors on CNR in single-exposure DE imaging with PCDs, (2) evaluated the accuracy of these models in predicting experimental trends, (3) quantified improvements in CNR achievable through ACNR and (4) determined the range of patient exposure rates at which pulse pile-up can be considered negligible. To the best of our knowledge, this study represents the first systematic investigation of single-exposure DE imaging of lung nodules with PCDs.

Development of a Monte Carlo simulation platform for the systematic evaluation of photon-counting detector-based micro-CT

PurposeThis study aimed to develop a photon-counting detector (PCD) based micro-CT simulation platform for assessing the performance of three different PCD sensor materials: cadmium telluride (CdTe), gallium arsenide (GaAs), and silicon (Si). The evaluation encompasses the components of primary and scatter signals, performance of imaging contrast agents, and detector efficiency. MethodsSimulations were performed using the Geant4 Monte Carlo toolkit, and a micro-PCD-CT system was meticulously modeled based on realistic geometric parameters. Results.The simulation can obtain HU values consistent with measured results for iodine and calcium hydroxyapatite contrast agents. The two major components of scatter signals for CdTe and GaAs based PCD are fluorescent X-ray photons and photoelectrons, whereas for Si, the components are photoelectrons and Compton electrons. Scattering counts of CdTe and GaAs sensors can be effectively reduced by using energy thresholds, whereas those of Si sensor are insensitive to the applied threshold. The optimal threshold values for CdTe and GaAs are 30 and 15 keV, respectively. For contrast agent imaging, GaAs exhibits enhanced sensitivity to low photon energies compared to CdTe, while it’s contrast-to-noise ratio (CNR) values are slightly lower than those of CdTe at the same contrast agent concentration. Among the three sensor materials, Si has the lowest CNR and detector efficiency; CdTe exhibits the highest efficiency, except in low-energy ranges (< 45 keV), where GaAs has superior efficiency. ConclusionsThe proposed methods are expected to benefit PCD optimization and applications, including energy threshold selection, scattering correction, and may reduce the need for large-scale experiments.

Optical Transparency Windows in Near-Infrared and Short-Wave Infrared for the Skin, Skull, and Brain: Fluorescence Bioimaging Using PbS Quantum Dots.

Fluorescence imaging (FI) employing near-infrared (NIR) light within the range of ~750-1350 nm enables biomedical imaging several millimeters beneath the tissue surface. More recent investigations into the short-wave IR (SWIR) transparency windows between ~1550-1870 and 2100-2300 nm highlight their superior capabilities. This research presents a comparison of IR-FI of PbS quantum dots, emitting at 990, 1310, and 1580 nm, through the mouse scalp skin, skull, and brain. The SWIR fluorescence is the most effectively transmitted signal, showing particularly significant enhancement when passing through the skull, which causes high light scattering. For the analysis of the imaging results and light propagation through the organs, their spectra of attenuation, absorption, and scattering coefficients are measured. In view of biomedical imaging, attenuation due to light scattering is a more destructive factor. Hence, the spatial resolution and imaging contrast can be improved by operating in SWIR due to decreased light scattering.

Hypoxia-Responsive Biomimetic Nanobubbles for Oxygen Delivery Promote Synergistic Ischemic Stroke Protection.

Effective, precise, and controllable oxygen delivery is crucial for regulating the oxygenation balance of brain tissue at the early stages of acute ischemic stroke (AIS) because the absence of oxygen may result in a series of highly interconnected vascular-neural pathological events, including oxidative stress, inflammation, and neuroapoptosis. In this study, platelet membrane-reassembled oxygen nanobubbles (PONBs) were constructed for oxygen delivery to protect AIS. Benefiting from the preserved natural targeting ability of platelet membranes, oxygen can be controlled release into the hypoxia lesion at the preperfusion stage due to vascular injury targeting and oxygen sustained diffusion capability after PONBs administration. Furthermore, synergizing with bioactive components carried by platelet membranes, PONBs can inhibit post-AIS vascular occlusion and maintain blood-brain barrier integrity, thereby facilitating enhanced oxygen delivery of PONBs, establishing a positive feedback loop between oxygen delivery and AIS protection. Additionally, the accumulation of PONBs enhances the ultrasound imaging contrast, enabling precise localization and dynamic monitoring of AIS lesions. Thus, PONBs represent a promising strategy for the diagnosis and treatment of AIS.

Cell membrane-functionalized bismuth oxyiodide nanodots as potential contrast agent for gastrointestinal tract imaging

Various noninvasive imaging modalities, including X-ray and computed tomography (CT) imaging, have provided significant advantages in accurately assessing the conditions of the gastrointestinal (GI) tract. The corresponding contrast agent with high resolution and biosafety is one of the most crucial focuses in the diagnosis of GI diseases. In this study, considering the requirements of good biocompatibility and biosafety, a novel imaging platform composed of the high-performance contrast agent based on macrophage membrane-coated BiOI nanodots (BiOI@M) was designed via a facile approach. The BiOI@M exhibited outstanding long-term stability and low toxicity. Significantly, BiOI@M demonstrated superior imaging ability compared to clinical barium sulfate. Higher CT values of BiOI@M were observed at equivalent concentrations to barium sulfate, thereby clearly outlining the stomach, small intestine, caecum, and colon after the oral administration of BiOI@M solutions in X-ray and CT imaging. Taken together, BiOI@M could serve as a novel efficient contrast agent in X-ray/CT imaging of the GI tract and diagnosis of GI diseases.

PEGylated Pemetrexed and PolyNIPAM Decorated Gold Nanoparticles: A Biocompatible and Highly Stable CT Contrast Agent for Cancer Imaging.

This study describes a multifunctional nanoparticle platform for targeted CT imaging and therapy of cancers. Pemetrexed (conjugated with polyethylene glycol, MW 2000 Da) and polyNIPAM (PEGylated) were designed for targeted delivery to folate receptors and thermally ablated tumors, respectively. These moieties were coated on gold nanoparticles (7 and 30 nm), and the prepared compounds were characterized using 1H NMR, FT-IR, CHNS, DLS, TEM, TGA, and UV-vis. The resulting agents exhibited 2-4 times higher X-ray attenuation compared to Visipaque and demonstrated specific accumulation in tumor tissue (4T1 xenograft model) 90 min after injection in mice. The nanoparticles displayed anticancer activity against 4T1 and MDA-MB-231 breast cancer cells (IC50: 182.87 and 206.18 μg/mL) and good biocompatibility. Importantly, the platform showed excellent stability over a year and at pH 2-12 and temperature range of -78 to 40 °C, and a water-dichloromethane extraction method was optimized for efficient purification, facilitating large-scale production.

Photon-counting CT for forensic death investigations-a glance into the future of virtual autopsy.

This article explores the potential of photon-counting computed tomography (CT) in forensic medicine for a range of forensic applications. Photon-counting CT surpasses conventional CT in several key areas. It boasts superior spatial and contrast resolution, enhanced image quality at low x-ray energies, and spectral imaging capabilities that enable more precise material differentiation. These advantages translate to superior visualization of bone structures, foreign bodies, and soft tissues in postmortem examinations. The article discusses the technical principles of photon-counting CT detectors and highlights its potential applications in forensic imaging, including high-resolution virtual autopsies, pediatric forensic CT, trauma analysis, and bone density measurements. Furthermore, advancements in vascular imaging and soft tissue contrast promise to propel CT-based death investigations to an even more prominent role. The article concludes by emphasizing the immense potential of this new technology in forensic medicine and anthropology.

Rotor proliferation promotes high-brightness AIE of iridium emitter accomplishing high-contrast luminous imaging of latent fingerprints to level 3 details

Luminous imaging of latent fingerprints (LFPs) necessitates the possession of high-brightness aggregation-state luminescence by developers to ensure sufficient imaging contrast and resolution. A novel strategy involving incremental rotor modification is presented for AIE activation of the iridium developer. The rotor proliferation prominently improves the rotational activity of groups and facilitates high-efficiency RIM, thereby prompting the AIE activation of iridium developer with high luminous efficiency. Subsequently, a prompt, high-contrast, and robust LFP imaging protocol is developed utilizing the high-brightness AIE-active iridium developer. This innovative protocol realizes the luminous imaging and quantification of microscopic features in fingerprint ridges and furrows, including ridge widths, edge morphology of ridges, included angles, pores, and pore pitches with exceptional imaging contrast and refined detail resolution. Moreover, it allows for accurate identification of individual traits across diverse substrates without any pre-/post-processing to LFPs. The high-brightness AIE-active iridium developer provides outstanding aging resistance to developed fingerprints, thereby strongly supporting the acquisition, transfer, and preservation of fingerprint evidence. The luminous imaging protocol of LFPs based on high-brightness AIE exhibits robust adaptability to actual scenes and offers a premium scheme for facilitating forensic investigation.

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.

Theranostics: aptamer-assisted carbon nanotubes as MRI contrast and photothermal agent for breast cancer therapy

Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character. The successful functionalization was confirmed by FTIR spectroscopy. Surface morphology changes were observed using SEM, while TEM confirmed the structural integrity of the MWCNTs after functionalization. Particle size, zeta potential, and UV spectroscopy were also performed to further characterize the nanoparticles. The breast cancer aptamer specific to Mucin-1 (MUC-1) was then conjugated with the functionalized MWCNTs. These MWCNTs successfully targeted breast cancer cells (MDA-MB-231) as examined by cellular uptake studies and exhibited a reduction in cancer-induced inflammation, as evidenced by gene transcription (qPCR) and protein expression (immunoblotting) levels. Immunoblot and confocal-based immunofluorescence assay (IFA) indicated the ability of CNTs to induce photothermal cell death of MDA-MB-231 cells. Upon imaging, cancer cells were effectively visualized due to the MWCNTs’ ability to act as magnetic resonance imaging (MRI) contrast agents. Additionally, MWCNTs demonstrated photothermal capabilities to eliminate bound cancer cells. Collectively, our findings pave the way for developing aptamer-labeled MWCNTs as viable “theranostic alternatives” for breast cancer treatment.Graphical abstract

Label-free 3D molecular imaging of living tissues using Raman spectral projection tomography

The ability to image tissues in three dimensions (3D) with label-free molecular contrast at the mesoscale would be a valuable capability in biology and biomedicine. Here, we introduce Raman spectral projection tomography (RSPT) for volumetric molecular imaging with optical sub-millimeter spatial resolution. We have developed a RSPT imaging instrument capable of providing 3D molecular contrast in transparent and semi-transparent samples. We also created a computational pipeline for multivariate reconstruction to extract label-free spatial molecular information from Raman projection data. Using these tools, we demonstrate imaging and visualization of phantoms of various complex shapes with label-free molecular contrast. Finally, we apply RSPT as a tool for imaging of molecular gradients and extracellular matrix heterogeneities in fixed and living tissue-engineered constructs and explanted native cartilage tissues. We show that there exists a favorable balance wherein employing Raman spectroscopy, with its advantages in live cell imaging and label-free molecular contrast, outweighs the reduction in imaging resolution and blurring caused by diffuse photon propagation. Thus, RSPT imaging opens new possibilities for label-free molecular monitoring of tissues.

Heating Induced Nanoparticle Migration and Enhanced Delivery in Tumor Treatment Using Nanotechnology.

Nanoparticles have been developed as imaging contrast agents, heat absorbers to confine energy into targeted tumors, and drug carriers in advanced cancer treatment. It is crucial to achieve a minimal concentration of drug-carrying nanostructures or to induce an optimized nanoparticle distribution in tumors. This review is focused on understanding how local or whole-body heating alters transport properties in tumors, therefore leading to enhanced nanoparticle delivery or optimized nanoparticle distributions in tumors. First, an overview of cancer treatment and the development of nanotechnology in cancer therapy is introduced. Second, the importance of particle distribution in one of the hyperthermia approaches using nanoparticles in damaging tumors is discussed. How intensive heating during nanoparticle hyperthermia alters interstitial space structure to induce nanoparticle migration in tumors is evaluated. The next section reviews major obstacles in the systemic delivery of therapeutic agents to targeted tumors due to unique features of tumor microenvironments. Experimental observations on how mild local or whole-body heating boosts systemic nanoparticle delivery to tumors are presented, and possible physiological mechanisms are explored. The end of this review provides the current challenges facing clinicians and researchers in designing effective and safe heating strategies to maximize the delivery of therapeutic agents to tumors.