Development of finely tuned liposome nanoplatform for macrophage depletion.

BACKGROUND: Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. RESULTS: We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. CONCLUSION: The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent.

Injectable biocompatible nanocomposites of Prussian blue nanoparticles and bacterial cellulose as a safe and effective photothermal cancer therapy.

Photothermal therapy (PTT) is a novel cancer treatment using a photoabsorber to cause hyperthermia to kill tumors by laser irradiation. Prussian blue nanoparticles (PB NPs) are considered as next-generation photothermal agents due to the facile synthesis and excellent absorption of near-infrared light. Although PB NPs demonstrate remarkable PTT capabilities, their clinical application is limited due to their systemic toxicity. Bacterial cellulose (BC) has been applied to various bio-applications based on its unique properties and biocompatibility. Herein, we design composites with PB NPs and BC as an injectable, highly biocompatible PTT agent (IBC-PB composites). Injectable bacterial cellulose (IBC) is produced through the trituration of BC, with PB NPs synthesized on the IBC surface to prepare IBC-PB composites. IBC-PB composites show in vitro and in vivo photothermal therapeutic effects similar to those of PB NPs but with significantly greater biocompatibility. Specifically, in vitro therapeutic index of IBC-PB composites is 26.5-fold higher than that of PB NPs. Furthermore, unlike PB NPs, IBC-PB composites exhibit no overt toxicity in mice as assessed by blood biochemical analysis and histological images. Hence, it is worth pursuing further research and development of IBC-PB composites as they hold promise as safe and efficacious PTT agents for clinical application.

Mannosylated-serum albumin nanoparticle imaging to monitor tumor-associated macrophages under anti-PD1 treatment.

BACKGROUND: Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD1) block tumor growth by reinvigorating the immune system; however, determining their efficacy only by the changes in tumor size may prove inaccurate. As the immune cells including macrophages in the tumor microenvironment (TME) are associated with the response to anti-PD1 therapy, tumor-associated macrophages (TAMs) imaging using nanoparticles can noninvasively provide the immune enrichment status of TME. Herein, the mannosylated-serum albumin (MSA) nanoparticle was labeled with radioactive isotope 68Ga to target the mannose receptors on macrophages for noninvasive monitoring of the TME according to anti-PD1 therapy. RESULTS: B16F10-Luc and MC38-Luc tumor-bearing mice were treated with anti-PD1, and the response to anti-PD1 was determined by the tumor volume. According to the flow cytometry, the responders to anti-PD1 showed an increased proportion of TAMs, as well as lymphocytes, and the most enriched immune cell population in the TME was also TAMs. For noninvasive imaging of TAMs as a surrogate of immune cell augmentation in the TME via anti-PD1, we acquired [68Ga] Ga-MSA positron emission tomography. According to the imaging study, an increased number of TAMs in responders at the early phase of anti-PD1 treatment was observed in both B16F10-Luc and MC38-Luc tumor-bearing mice models. CONCLUSION: As representative immune cells in the TME, non-invasive imaging of TAMs using MSA nanoparticles can reflect the immune cell enrichment status in the TME closely associated with the response to anti-PD1. As non-invasive imaging using MSA nanoparticles, this approach shows a potential to monitor and evaluate anti-tumor response to immune checkpoint inhibitors.

Limited power of dopamine transporter mRNA mapping for predicting dopamine transporter availability.

Dopamine transporters (DAT) are transmembrane proteins that translocate dopamine from the extracellular space into presynaptic neurons. We aimed to investigate the predictive power of DAT mRNA for DAT protein expression, measured using positron emission tomography (PET). We performed 18 F-FP-CIT PET scans in 35 healthy individuals. Binding potentials (BPND ) from the ventral striatum, caudate nucleus, putamen, and middle frontal, orbitofrontal, cingulate, parietal, and temporal cortices were measured. DAT gene expression data were obtained from the freely available Allen Human Brain Atlas derived from six healthy donors. The auto-correlation of PET-derived BPND s for DAT was intermediate (mean ρ2  = .66) with ρ2 ranging from .0811 to 1. However, the auto-correlation of mRNA expression was weak across the probes with a mean ρ2 of .09-.23. Cross-correlations between PET-derived BPND s and mRNA expression were weak with a mean ρ2 ranging from 0 to .22 across the probes. In conclusion, we observed weak associations between DAT mRNA expression and DAT availability in human brains. Therefore, DAT mRNA mapping may have only limited predictive power for DAT availability in humans. However, the difference in distribution of DAT mRNA and DAT protein may influence this limitation.

Development of theranostic dual-layered Au-liposome for effective tumor targeting and photothermal therapy.

BACKGROUND: Photothermal therapy (PTT) is an emerging anti-cancer therapeutic strategy that generates hyperthermia to ablate cancer cells under laser irradiation. Gold (Au) coated liposome (AL) was reported as an effective PTT agent with good biocompatibility and excretory property. However, exposed Au components on liposomes can cause instability in vivo and difficulty in further functionalization. RESULTS: Herein, we developed a theranostic dual-layered nanomaterial by adding liposomal layer to AL (LAL), followed by attaching polyethylene glycol (PEG) and radiolabeling. Functionalization with PEG improves the in vivo stability of LAL, and radioisotope labeling enables in vivo imaging of LAL. Functionalized LAL is stable in physiological conditions, and 64Cu labeled LAL (64Cu-LAL) shows a sufficient blood circulation property and an effective tumor targeting ability of 16.4%ID g-1 from in vivo positron emission tomography (PET) imaging. Also, intravenously injected LAL shows higher tumor targeting, temperature elevation in vivo, and better PTT effect in orthotopic breast cancer mouse model compared to AL. The tumor growth inhibition rate of LAL was 3.9-fold higher than AL. CONCLUSION: Based on these high stability, in vivo imaging ability, and tumor targeting efficiency, LAL could be a promising theranostic PTT agent.

Striatal dopamine transporter changes after glucose loading in humans.

AIMS: The dopamine transporter (DAT) actively translocates dopamine that is released from the presynaptic neurons across the membranes of nerve terminals into the extracellular space. We hypothesized that glucose loading-induced changes in striatal DAT levels could be associated with food intake in humans. MATERIALS AND METHODS: An intravenous bolus injection of 18 F-FP-CIT was administered after infusion of glucose or placebo (normal saline), and emission data were acquired over 90 minutes in 33 healthy males. For a volume-of-interest-based analysis, an atlas involving sub-striatal regions of ventral striatum (VST), caudate nucleus and putamen was applied. DAT availability and binding potential (BPND ) were measured using a simplified reference tissue method with cerebellum as the reference. RESULTS: The glucose-loaded BPND from the VST negatively correlated with body mass index (BMI), whereas the placebo-loaded BPND from the VST did not. After loading with glucose, there were substantial increases in BPND s: 18.3%, 71.7% and 34.0% on average in the VST, caudate nucleus and putamen, respectively. CONCLUSION: Striatal DAT changes after glucose loading, and BMI is associated with glucose-loaded DAT availability, not with placebo-loaded DAT availability. DAT might have a role in the reward system of eating behavior.

Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme.

Radiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date.

Development of 99mTc-Labeled Human Serum Albumin with Prolonged Circulation by Chelate-then-Click Approach: A Potential Blood Pool Imaging Agent.

Technetium-99m-labeled human serum albumin (99mTc-HSA) has been utilized as a blood pool imaging agent in the clinic for several decades. However, 99mTc-HSA has a short circulation time, which is a critical shortcoming for a blood pool imaging agent. Herein, we developed a novel 99mTc-labeled HSA with a long circulation time using click chemistry and a chelator, 2,2'-dipicolylamine (DPA), (99mTc-DPA-HSA). Specifically, we examined the feasibility of copper-free strain-promoted alkyne-azide cycloaddition (SPAAC) for the incorporation of HSA to the [99mTc (CO)3(H2O)3]+ system by adopting a chelate-then-click approach. In this strategy, a potent chelate system, azide-functionalized DPA, was first complexed with [99mTc (CO)3(H2O)3]+, followed by the SPAAC click reaction with azadibenzocyclooctyne-functionalized HSA (ADIBO-HSA) under biocompatible conditions. Radiolabeling efficiency of azide-functionalized DPA (99mTc-DPA) was >98%. Click conjugation efficiency of 99mTc-DPA with ADIBO-HSA was between 76 and 99% depending on the number of ADIBO moieties attached to HSA. In whole-body in vivo single photon emission computed tomography images, the blood pool uptakes of 99mTc-DPA-HSA were significantly enhanced compared to those of 99mTc-HSA at 10 min, 2, and 6 h after the injection ( P < 0.001, 0.025, and 0.003, respectively). Furthermore, the blood activities of 99mTc-DPA-HSA were 8 times higher at 30 min and 10 times higher at 3 h after the injection compared to those of conventional 99mTc-HSA in ex vivo biodistribution experiment. The results exhibit the potential of 99mTc-DPA-HSA as a blood pool imaging agent and further illustrate the promise of the pre-labeling SPAAC approach for conjugation of heat-sensitive biological targeting vectors with [99mTc (CO)3(H2O)3]+.

Prognostic Value of Metabolic and Volumetric Parameters of FDG PET in Pediatric Osteosarcoma: A Hypothesis-generating Study.

Purpose To preliminarily assess the potential prognostic value of various fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters before, during, and after neoadjuvant chemotherapy (NCT). Materials and Methods Thirty-four patients with osteosarcoma were enrolled prospectively from 2008 to 2012 and underwent FDG PET/computed tomography (CT) imaging before (baseline scan), during (interim scan) and after NCT (posttherapy scan). The study was approved by the institutional review board and informed consent was received from patients. Maximum and peak standardized uptake value (SUVmax and SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Predictive value of FDG PET parameters for event-free survival (EFS) and overall survival (OS) were evaluated. Multivariable Cox regression analysis for EFS and OS was performed by using histologic response and initial presence of metastasis as covariates. Results At baseline scan, SUVpeak, MTV, and TLG were predictive of EFS (P = .006-.03) and OS (P = .001-.03) but not associated with histologic response. At interim and posttherapy scan, SUVmax, SUVpeak, MTV, and TLG were associated with histologic response (P = .0002-.04) and predictive of EFS (P = .004-.02) and OS (P = .001-.03). Multivariable Cox regression analysis revealed that the FDG PET parameters either at baseline, interim, or posttherapy were independently predictive of EFS and OS. In particular, baseline MTV was an independent predictor of EFS (hazard ratio, 5.0 [95% confidence interval {CI}: 1.5, 16.8]) and OS (hazard ratio, 29.4 [95% CI: 2.2, 392.2]). Conclusion SUVpeak, MTV, and TLG either at baseline, interim, or posttherapy were predictive of EFS and OS and may be useful prognostic biomarkers for osteosarcoma. © RSNA, 2018 Online supplemental material is available for this article.

Renal-Clearable PEGylated Porphyrin Nanoparticles for Image-guided Photodynamic Cancer Therapy.

Noninvasive dynamic positron emission tomography (PET) imaging was used to investigate the balance between renal clearance and tumor uptake behaviors of polyethylene glycol (PEG)-modified porphyrin nanoparticles (TCPP-PEG) with various molecular weights. TCPP-PEG10K nanoparticles with clearance behavior would be a good candidate for PET image-guided photodynamic therapy.

Radiolabeled pertuzumab for imaging of human epidermal growth factor receptor 2 expression in ovarian cancer.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) is over-expressed in over 30% of ovarian cancer cases, playing an essential role in tumorigenesis and metastasis. Non-invasive imaging of HER2 is of great interest for physicians as a mean to better detect and monitor the progression of ovarian cancer. In this study, HER2 was assessed as a biomarker for ovarian cancer imaging using 64Cu-labeled pertuzumab for immunoPET imaging. METHODS: HER2 expression and binding were examined in three ovarian cancer cell lines (SKOV3, OVCAR3, Caov3) using in vitro techniques, including western blot and saturation binding assays. PET imaging and biodistribution studies in subcutaneous models of ovarian cancer were performed for non-invasive in vivo evaluation of HER2 expression. Additionally, orthotopic models were employed to further validate the imaging capability of 64Cu-NOTA-pertuzumab. RESULTS: HER2 expression was highest in SKOV3 cells, while OVCAR3 and Caov3 displayed lower HER2 expression. 64Cu-NOTA-pertuzumab showed high specificity for HER2 (Ka = 3.1 ± 0.6 nM) in SKOV3. In subcutaneous tumors, PET imaging revealed tumor uptake of 41.8 ± 3.8, 10.5 ± 3.9, and 12.1 ± 2.3%ID/g at 48 h post-injection for SKOV3, OVCAR3, and Caov3, respectively (n = 3). In orthotopic models, PET imaging with 64Cu-NOTA-pertuzumab allowed for rapid and clear delineation of both primary and small peritoneal metastases in HER2-expressing ovarian cancer. CONCLUSIONS: 64Cu-NOTA-pertuzumab is an effective PET tracer for the non-invasive imaging of HER2 expression in vivo, rendering it a potential tracer for treatment monitoring and improved patient stratification.

ImmunoPET Imaging of Insulin-Like Growth Factor 1 Receptor in a Subcutaneous Mouse Model of Pancreatic Cancer.

The role of insulin-like growth factor-1 receptor (IGF-1R) in cancer tumorigenesis was established decades ago, yet there are limited studies evaluating the imaging and therapeutic properties of anti-IGF-1R antibodies. Noninvasive imaging of IGF-1R may allow for optimized patient stratification and monitoring of therapeutic response in patients. Herein, this study reports the development of a Zirconium-89 ((89)Zr)-labeled anti-IGF-1R antibody ((89)Zr-Df-1A2G11) for PET imaging of pancreatic cancer. Successful chelation and radiolabeling of the antibody resulted in a highly stable construct that could be used for imaging IGF-1R expressing tumors in vivo. Western blot and flow cytometry studies showed that MIA PaCa-2, BxPC-3, and AsPC-1 pancreatic cancer cell lines expressed high, moderate, and low levels of IGF-1R, respectively. These three pancreatic cancer cell lines were subcutaneously implanted into mice. By employing the PET imaging technique, the tumor accumulation of (89)Zr-Df-1A2G11 was found to be dependent on the level of IGF-1R expression. Tumor accumulation of (89)Zr-Df-1A2G11 was 8.24 ± 0.51, 5.80 ± 0.54, and 4.30 ± 0.42 percentage of the injected dose (%ID/g) in MIA PaCa-2, BxPC-3, and AsPC-1-derived tumor models at 120 h postinjection, respectively (n = 4). Biodistribution studies and ex vivo immunohistochemistry confirmed these findings. In addition, (89)Zr-labeled nonspecific human IgG ((89)Zr-Df-IgG) displayed minimal uptake in IGF-1R positive MIA PaCa-2 tumor xenografts (3.63 ± 0.95%ID/g at 120 h postinjection; n = 4), demonstrating that (89)Zr-Df-1A2G11 accumulation was highly specific. This study provides initial evidence that our (89)Zr-labeled IGF-1R-targeted antibody may be employed for imaging a wide range of malignancies. Antibodies may be tracked in vivo for several days to weeks with (89)Zr, which may enhance image contrast due to decreased background signal. In addition, the principles outlined in this study can be employed for identifying patients that may benefit from anti-IGF-1R therapy.

Prognostic value of volumetric parameters of (18)F-FDG PET in non-small-cell lung cancer: a meta-analysis.

PURPOSE: We conducted a comprehensive systematic review of the literature on volumetric parameters from (18)F-FDG PET and a meta-analysis of the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in patients with lung cancer. METHODS: A systematic search of MEDLINE and EMBASE was performed using the keywords "positron emission tomography (PET)", "lung cancer", and "volume". Inclusion criteria were: (18)F-FDG PET used as an initial imaging tool; studies limited to non-small-cell lung cancer (NSCLC); volume measurement of lung cancer; patients who had not undergone surgery, chemotherapy, or radiotherapy before the PET scan; and studies that reported survival data. Event-free survival and overall survival were evaluated as outcomes. The impact of MTV and TLG on survival was measured in terms of the hazard ratio (HR) effect size. Data from each study were analysed using Review Manager 5.2. RESULTS: Thirteen eligible studies including 1,581 patients were analysed. Patients with high MTV showed a worse prognosis with an HR of 2.71 (95% CI 1.82 - 4.02, p < 0.00001) for adverse events and an HR of 2.31 (95% CI 1.54 - 3.47, p < 0.00001) for death. Patients with high TLG also showed a worse prognosis with an HR of 2.35 (95% CI 1.91 - 2.89, p < 0.00001) for adverse events and an HR of 2.43 (95% CI 1.89 - 3.11, p < 0.00001) for death. The prognostic value of MTV and TLG remained significant in a subgroup analysis according to TNM stage as well as the methods for defining cut-off values and tumour delineation. CONCLUSION: Volumetric parameters from (18)F-FDG PET are significant prognostic factors for outcome in patients with NSCLC. Patients with a high MTV or TLG are at higher risk of adverse events and death. MTV and TLG were significant prognostic factors in patients with TNM stage I/II and stage III/IV NSCLC.

Radionanomedicine: widened perspectives of molecular theragnosis.

Despite of promising preclinical results in the fields of in vivo theragnostics of nanomedicine, a majority of attempt for clinical translation has been blocked by unsolved concerns about possible hazards to human body. Theragnosis of nanomedicine relies on the property of huge surface area to volume ratio of nanomaterials, which can offer potential for multi-functionality. Radionanomedicine has a hybrid characteristic of tracer technology and multi-functionality. Thus, key advantage of radionanomedicine is a possibility of using low amount of nanomaterials for theragnosis. This review article focuses on the concept and advantages of radionanomedicine in theragnosis, formulation of radionanomaterials (particularly encapsulation method), in vivo biodistribution and excretion of radionanomaterials, and immune responses to radionanomaterials. FROM THE CLINICAL EDITOR: The expansion of nanomedicine has recently seen the development of a new branch - radionanomedicine. The core concept of radionanomedicine relies on the labeling of radionuclides onto nanomaterials for use both in diagnosis and therapy. In this article, the authors gave a comprehensive review on the current status of radionanomedicine. This should provide interesting reading for practicing clinicians.

Identifying neuropathic pain using (18)F-FDG micro-PET: a multivariate pattern analysis.

Pain is a multidimensional experience emerging from the flow of information between multiple brain regions. A growing body of evidence suggests that pathological pain causes plastic changes of various brain regions. Here, we hypothesized that the induction of neuropathic pain alters distributed patterns of the resting-state brain activity in animal models, and capturing the altered pattern would enable identification of neuropathic pain at the individual level. We acquired micro-positron emission tomography with [(18)F]fluorodeoxyglucose (FDG micro-PET) images in awake rats with spinal nerve ligation (SNL) and without (sham) (SNL group, n=13; sham group, n=10). Multivariate pattern analysis (MVPA) with linear support vector machine (SVM) successfully identified the brain with SNL (92.31% sensitivity, 90.00% specificity, and 91.30% total accuracy). Predictive brain regions with increased metabolism were mainly located in prefrontal-limbic-brainstem areas including the anterior olfactory nucleus (AON), insular cortex (IC), piriform cortex (PC), septal area (SA), basal forebrain/preoptic area (BF/POA), amygdala (AMY), hypothalamus (HT), rostral ventromedial medulla (RVM) and the ventral midbrain (VMB). In contrast, predictive regions with decreased metabolism were observed in widespread cortical areas including secondary somatosensory cortex (S2), occipital cortex (OC), temporal cortex (TC), retrosplenial cortex (RSC), and the cerebellum (CBL). We also applied the univariate approach and obtained reduced prediction performance compared to MVPA. Our results suggest that developing neuroimaging-based diagnostic tools for pathological pain can be achieved by considering patterns of the resting-state brain activity.

Abnormal metabolic connectivity in the pilocarpine-induced epilepsy rat model: a multiscale network analysis based on persistent homology.

Temporal lobe epilepsy is associated with dysfunctional brain networks. Here we investigated metabolic connectivity in the pilocarpine-induced epilepsy rat model and applied a new multiscale framework to the analysis of metabolic networks of small-animal brains. [(18)F]fluorodeoxyglucose PET was acquired in pilocarpine-induced chronic epilepsy rats and controls to yield interregional metabolic correlation by inter-subject manner. When interregional correlation of epilepsy rats and controls was compared directly, the epilepsy rats showed reduced connectivity involving the left amygdala and left entorhinal cortex. When regional graph properties were calculated to characterize abnormal nodes in the epileptic brain network, the epilepsy rats showed reduced nodal and local efficiencies in the left amygdala. Then, a new multiscale framework, persistent brain network homology, was used to examine metabolic connectivity with a threshold-free approach and the difference between two networks was analyzed using single linkage distances (SLDs) of all pairwise nodes. We found a tendency for longer SLDs between the left insula/left amygdala and bilateral cortical/subcortical structures in the epilepsy rats. Persistent brain network homology analysis as well as interregional correlation study implied the abnormal left limbic-paralimbic-neocortical network in the pilocarpine-induced epilepsy rat models. In conclusion, we found a globally disrupted network in the epileptic brain in rats, particularly in the limbic and paralimbic structures by direct comparison, graph properties and multiscale network analysis. These results demonstrate that the multiscale and threshold-free network analysis can be used to find the network abnormality in small-animal brains as a preclinical research.

In vivo brain delivery of v-myc overproduced human neural stem cells via the intranasal pathway: tumor characteristics in the lung of a nude mouse.

We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc) were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%), and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%). In the mice with initial lung signals (4 of 9, 44.4%), the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

Development of Indocyanine Green/Methyl-ß-cyclodextrin Complex-Loaded Liposomes for Enhanced Photothermal Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-ß-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.

In vivo visualization and monitoring of viable neural stem cells using noninvasive bioluminescence imaging in the 6-hydroxydopamine-induced mouse model of Parkinson disease.

Transplantation of neural stem cells (NSCs) has been proposed as a treatment for Parkinson disease (PD). The aim of this study was to monitor the viability of transplanted NSCs expressing the enhanced luciferase gene in a mouse model of PD in vivo. The PD animal model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA). The behavioral test using apomorphine-induced rotation and positron emission tomography with [18F]N-(3-fluoropropyl)-2'-carbomethoxy-3'-(4-iodophenyl)nortropane ([18F]FP-CIT) were conducted. HB1.F3 cells transduced with an enhanced firefly luciferase retroviral vector (F3-effLuc cells) were transplanted into the right striatum. In vivo bioluminescence imaging was repeated for 2 weeks. Four weeks after transplantation, [18F]FP-CIT PET and the rotation test were repeated. All 6-OHDA-injected mice showed markedly decreased [18F]FP-CIT uptake in the right striatum. Transplanted F3-effLuc cells were visualized on the right side of the brain in all mice by bioluminescence imaging. The bioluminescence intensity of the transplanted F3-effLuc cells gradually decreased until it was undetectable by 10 days. The behavioral test showed that stem cell transplantation attenuated the motor symptoms of PD. No significant change was found in [18F]FP-CIT imaging after cell transplantation. We successfully established an in vivo bioluminescence imaging system for the detection of transplanted NSCs in a mouse model of PD. NSC transplantation induced behavioral improvement in PD model mice.

18F-FDG PET/CT in the Management of Osteosarcoma.

Osteosarcoma is the most common type of primary malignant bone tumor. 18F-FDG PET/CT is useful for staging, detecting recurrence, monitoring response to neoadjuvant chemotherapy, and predicting prognosis. Here, we review the clinical aspects of osteosarcoma management and assess the role of 18F-FDG PET/CT, in particular with regard to pediatric and young adult patients.