Mei Tian

Response of osteogenic sarcoma to neoadjuvant therapy: evaluated by 18F-FDG-PET

ObjectiveThe aim of this study was to evaluate the potential role of F-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in assessing the chemotherapy response of osteosarcoma when compared with histologically assessed tumor necrosis.MethodsFifteen patients were examined with whole-body FDG-PET prior to and following neoadjuvant therapy. The maximum standard uptake value (SUVmax) of tumor and tumor to background ratio (TBR) prior to and following chemotherapy was used for semiquantitative PET imaging analysis. The SUVmax of prechemotherapy and post-chemotherapy was recorded as SUV1 and SUV2. TBR1 and TBR2 represented prechemotherapy and post-chemotherapy TBR. TBR was calculated by drawing an identical region of interest over the tumor and the contralateral normal limb or pelvis. Tumor necrosis was classified according to Salzer-Kuntschik’s criteria.ResultsEight patients with more than 90% tumor necrosis were classified as showing good responses and seven patients with less than 90% tumor necrosis as showing poor responses. SUV2/SUV1, TBR2/TBR1, and TBR2 were significantly correlated with the tumor necrosis degree (P < 0.01, P < 0.001, P < 0.001). TBR2/TBR1 were below 0.46 in all the patients with favorable responses, and higher than 0.49 in all the patients with unfavorable responses. However, it was difficult to distinguish good responses from poor responses by SUV2/SUV1.ConclusionsFDG-PET is a promising tool to assess the chemotherapy response of osteosarcoma noninvasively. The TBR was better than SUVmax in evaluating the chemotherapy response in this study.

A Comparative Study of Radiolabeled Bombesin Analogs for the PET Imaging of Prostate Cancer

Radiolabeled bombesin (BBN) analogs that bind to the gastrin-releasing peptide receptor (GRPR) represent a topic of active investigation for the development of molecular probes for PET or SPECT of prostate cancer (PCa). RM1 and AMBA have been identified as the 2 most promising BBN peptides for GRPR-targeted cancer imaging and therapy. In this study, to develop a clinically translatable BBN-based PET probe, we synthesized and evaluated 18F-AlF- (aluminum-fluoride) and 64Cu-radiolabeled RM1 and AMBA analogs for their potential application in PET imaging of PCa. Methods: 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)–conjugated RM1 and AMBA were synthesized and tested for their GRPR-binding affinities. The NODAGA-RM1 and NODAGA-AMBA probes were further radiolabeled with 64Cu or 18F-AlF and then evaluated in a subcutaneous PCa xenograft model (PC3) by small-animal PET imaging and biodistribution studies. Results: NODAGA-RM1 and NODAGA-AMBA can be successfully synthesized and radiolabeled with 64Cu and 18F-AlF. 64Cu- and 18F-AlF-labeled NODAGA-RM1 demonstrated excellent serum stability and tumor-imaging properties in the in vitro stability assays and in vivo imaging studies. 64Cu-NODAGA-RM1 exhibited tumor uptake values of 3.3 ± 0.38, 3.0 ± 0.76, and 3.5 ± 1.0 percentage injected dose per gram of tissue (%ID/g) at 0.5, 1.5, and 4 h after injection, respectively. 18F-AlF-NODAGA-RM1 exhibited tumor uptake values of 4.6 ± 1.5, 4.0 ± 0.87, and 3.9 ± 0.48 %ID/g at 0.5, 1, and 2 h, respectively. Conclusion: The high-stability, efficient tumor uptake and optimal pharmacokinetic properties highlight 18F-AlF-NODAGA-RM1 as a probe with great potential and clinical application for the PET imaging of prostate cancer.

PET imaging reveals brain functional changes in internet gaming disorder

BackgroundInternet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D2 (D2)/Serotonin 2A (5-HT2A) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D2 receptor and glucose metabolism.MethodsTwelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and 11C-N-methylspiperone (11C-NMSP) to assess the availability of D2/5-HT2A receptors and with 18F-fluoro-D-glucose (18F-FDG) to assess regional brain glucose metabolism, a marker of brain function. 11C-NMSP and 18F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states.ResultsIn internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D2 receptors was observed in the striatum, and was correlated to years of overuse. A low level of D2 receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex.ConclusionsFor the first time, we report the evidence that D2 receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D2/5-HT2A receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects.

Copper-Based Nanomaterials for Cancer Imaging and Therapy

Copper based nanoparticles (NPs) have attracted increased attention for biomedical applications. Copper chalcogenide NPs exhibit strong absorption in near-infrared region, demonstrate highly efficient light-to-heat transformation under near-infrared laser irradiation, and cause selective thermal destruction to the tumor. Smaller copper NPs display fluorescence signal and capability for optical imaging. Copper based NPs also serve as a versatile vehicle for drug delivery and image-guided therapy. This review covers recent advances related to the biomedical application of copper based NPs, with a focus on cancer imaging and therapy. We also discuss challenges to their successful clinical translation.

PET Demonstrates Functional Recovery After Transplantation of Induced Pluripotent Stem Cells in a Rat Model of Cerebral Ischemic Injury

The purpose of this study was to determine the functionality of the transplanted induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) in a rat model of cerebral ischemia with use of 18F-FDG small-animal PET imaging. Methods: Middle cerebral artery occlusion was used to establish cerebral ischemia. Twenty-four male rats were randomly assigned to 1 of 3 groups: iPSC treatment, ESC treatment, and the control phosphate-buffered saline (PBS) injection. After neurologic function tests and baseline 18F-FDG small-animal PET had been performed, 1.0 × 106 suspended iPSCs or ESCs were injected stereotactically into the left lateral ventricle. The treatment response was evaluated weekly by 18F-FDG PET scans and neurologic function tests. Histologic analyses and autoradiographic imaging were performed 4 wk after stem cell transplantation. Results: Compared with the PBS injection group, higher 18F-FDG accumulation in the ipsilateral cerebral infarction was observed in both the iPSC and the ESC treatment groups during the 4-wk period (P < 0.05). 18F-FDG accumulation in the ipsilateral cerebral infarction increased steadily over time in the iPSC treatment group. At 1 and 2 wk after stem cell transplantation, significant recovery of glucose metabolism was found in the ESC treatment group (P < 0.05) and then decreased gradually. The neurologic score in both stem cell–treated groups was significantly lower than that in the PBS group, indicating functional improvement. Immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated close to the ischemic region, and most of the stem cells expressed protein markers for cells of interest. Conclusion: 18F-FDG small-animal PET demonstrated metabolic recovery after iPSC and ESC transplantation in the rat model of cerebral ischemia. iPSCs could be considered a potentially better therapeutic approach than ESCs and are worthy of further translational investigation.

Theranostic CuS nanoparticles targeting folate receptors for PET image-guided photothermal therapy

Copper sulfide nanoparticles (CuS NPs) have been reported as a single-compartment theranostic nanosystem to visualize and treat tumors simultaneously. However, few studies have investigated the in vivo tumor-targeted delivery of this class of nanoparticles. In this study, we introduced a tumor-specific targeting ligand, folic acid (FA), onto the surface of CuS NPs as a model system to demonstrate the feasibility of actively targeted CuS NPs for positron emission tomography (PET) imaging and PET image-guided photothermal therapy (PTT). A one-pot synthetic method was used for introducing FA to CuS NPs to yield FA-CuS NPs. Biodistribution studies in mice bearing folate receptor-expressing KB tumor showed significantly higher tumor uptake of FA-CuS NPs than non-targeted polyethylene glycol (PEG)-coated PEG-CuS NPs after intravenous injection. Moreover, tumor uptake of FA-CuS NPs could be effectively blocked by free FA. Biodistribution and clearance of 64Cu-labeled FA-CuS NPs (FA-[64Cu]CuS NPs) could be readily visualized by microPET (μPET), which confirmed a significantly higher level of tumor uptake of FA-[64Cu]CuS NPs than non-targeted PEG-[64Cu]CuS NPs. μPET image-guided PTT with FA-CuS NPs mediated substantially greater tumor damage compared with PTT mediated by PEG-CuS NPs. Thus, FA-CuS NPs is a promising candidate for PTT of folate receptor-positive tumors.

Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model

Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([(64)Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [(64)Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy.

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

AbstractMajor depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD.

PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury

This study aimed to investigate neuroprotection of Danhong injection (DHI) in a rat model of cerebral ischemia using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU) group, DHI-1 group (DHI 1 mL/kg/d), DHI-2 group (DHI 2 mL/kg/d), and DHI-4 group (DHI 4 mL/kg/d). AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA). Levels of mature neuronal marker (NeuN), glial marker (GFAP), vascular density factor (vWF), and glucose transporter 1 (GLUT1) were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with 18F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

Molecular and Functional Imaging of Internet Addiction

Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) and single photon emission computed tomography (SPECT). MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC) could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects. Further investigations are needed to determine specific changes in the Internet addictive brain, as well as their implications for behavior and cognition.