Perspective in Nuclear Theranostics Using Exosome for the Brain / 대한핵의학회잡지

Owing to its highly biocompatible property as naturally produced nanoscale particle and drug carrying ability, exosome has attracted much interest in the biomedical area. Versatile functions of exosome in biological system play an important role in elucidating mysterious and unknown biological processes and pathological disease progression. For usage of exosome as brain disease therapeutics, even though the ability of exosomes crossing blood brain barrier (BBB) is not well clearly proven, the small size and their own characteristics possessing cell-derived molecular contents may provide great and beneficial tools for brain delivery and brain-associated disease therapy. A variety of trials related to bioapplications using stem cell-derived exosome in regenerative therapy or autologous exosome shuttling inhibitor targeting brain disease-associated protein marker enhance possibility of exosome toward clinical application. The radionuclide PETor SPECT imaging of radiolabeled exosome will be clearly able to provide accurate clues for analyzing their whole body distribution, targeting efficacy, and the degree of non-specific tissue uptake. In this perspective, the practical information on thranostics of exosome for brain delivery and therapy is offered and radionuclide-based exosome applicability will be dealt with.

Perspective in Nuclear Theranostics Using Exosome for the Brain / 대한핵의학회잡지

Owing to its highly biocompatible property as naturally produced nanoscale particle and drug carrying ability, exosome has attracted much interest in the biomedical area. Versatile functions of exosome in biological system play an important role in elucidating mysterious and unknown biological processes and pathological disease progression. For usage of exosome as brain disease therapeutics, even though the ability of exosomes crossing blood brain barrier (BBB) is not well clearly proven, the small size and their own characteristics possessing cell-derived molecular contents may provide great and beneficial tools for brain delivery and brain-associated disease therapy. A variety of trials related to bioapplications using stem cell-derived exosome in regenerative therapy or autologous exosome shuttling inhibitor targeting brain disease-associated protein marker enhance possibility of exosome toward clinical application. The radionuclide PETor SPECT imaging of radiolabeled exosome will be clearly able to provide accurate clues for analyzing their whole body distribution, targeting efficacy, and the degree of non-specific tissue uptake. In this perspective, the practical information on thranostics of exosome for brain delivery and therapy is offered and radionuclide-based exosome applicability will be dealt with.

Radio-graphene in Theranostic Perspectives / 대한핵의학회잡지

Owing to its unique physicochemical properties such as high surface area, notable biocompatibility, robust mechanical strength, high thermal conductivity, and ease of functionalization, 2D-layered graphene has received tremendous attention as a futuristic nanomaterial and its-associated research has been rapidly evolving in a variety of fields.With the remarkable advances of graphene especially in the biomedical realm, in vivo evaluation techniques to examine in vivo behavior of graphene are largely demanded under the hope of clinical translation. Many different types of drugs such as the antisense oligomer and chemotherapeutics require optimal delivery conveyor and graphene is now recognized as a suitable candidate due to its simple and high drug loading property. Termed as ‘ radio-graphene’, radioisotope-labeled graphene approach was recently harnessed in the realm of biomedicine including cancer diagnosis and therapy, contributing to the acquisition of in vivo information for targeted drug delivery. In this review, we highlight current examples for bioapplication of radiolabeled graphene with brief perspectives on future strategies in its extensive bio- or clinical applications.

Ultrasonographic Diaphragmatic Motion Analysis and Its Correlation With Pulmonary Function in Hemiplegic Stroke Patients

OBJECTIVE: To evaluate diaphragmatic motion via M-mode ultrasonography and to correlate it with pulmonary function in stroke patients. METHODS: This was a preliminary study comprised of ten stroke patients and sixteen healthy volunteers. The M-mode ultrasonographic probe was positioned in the subcostal anterior region of the abdomen for transverse scanning of the diaphragm during quiet breathing, voluntary sniffing, and deep breathing. We analyzed diaphragmatic motion and the relationship between diaphragmatic motion and pulmonary function. RESULTS: All stroke patients had restrictive pulmonary dysfunction. Compared to that exhibited by control subjects, stroke patients exhibited a significant unilateral reduction in motion on the hemiplegic side, primarily during volitional breathing. Diaphragmatic excursion in right-hemiplegic patients was reduced on both sides compared to that in control subjects. However, diaphragmatic excursion was reduced only on the left side and increased on the right side in left-hemiplegic patients compared to that in control subjects. Left diaphragmatic motion during deep breathing correlated positively with forced vital capacity (rho=0.86, p=0.007) and forced expiratory volume in 1 second (rho=0.79, p=0.021). CONCLUSION: Reductions in diaphragmatic motion and pulmonary function can occur in stroke patients. Thus, this should be assessed prior to the initiation of rehabilitation therapy, and M-mode ultrasonography can be used for this purpose. It is a non-invasive method providing quantitative information that is correlated with pulmonary function.

Usefulness of Videofluoroscopic Swallow Study in Treacher Collins Syndrome With Cleft Palate: A Case Report

A 3-year-old girl had multiple anomalies compatible with Treacher Collins Syndrome (TCS). From the neonatal period, sucking was poor, making tube feeding necessary. Excessive saliva was retained in the oral cavity. Nasal leakage caused by the cleft palate was observed when she spoke. The initial videofluoroscopic swallow study (VFSS) showed a poor posterior bolus transit and nasopharyngeal regurgitation. A delayed swallow reflex and bolus stasis at the vallecular and pyriform sinuses were recognized. Based on the VFSS findings, the patient underwent palatoplasty at 20 months of age. At approximately 23 months of age, a follow-up VFSS was performed; poor posterior bolus transit, nasopharyngeal regurgitation, and delayed swallow reflex were not observed. Finally, the patient was able to eat ground or chopped foods and solid foods orally. We deem VFSS to be helpful in deciding the appropriate management of dysphagia in TCS.

Evaluation of Cat Brain Infarction Model Using MicroPET / 대한핵의학회잡지

PURPOSE: PET has some disadvantage in the imaging of small animal due to poor resolution. With the advent of microPET scanner, it is possible to image small animals. However, the image quality was not good enough as human image. Due to larger brain, cat brain imaging was superior to mouse or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. MATERIALS AND METHODS: Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 microliter was injected using 30 G needle for 5 minutes to establish the infarction model. 18F-FDG microPET (Concorde Microsystems Inc., Knoxville, TN) scans were performed 1, 11 and 32 days after the infarction. In addition, 18F-FDG PET scans were performed using human PET scanner (Gemini, Philips medical systems, CA, USA) 13 and 47 days after the infarction. RESULTS: Two cat brain infarction models were established. The glucose metabolism of an infarction lesion improved with time. An infarction lesion was also distinguishable in the human PET scan. CONCLUSION: We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using 18F-FDG microPET scanner.

Development of Dual Reporter System of Mutant Dopamine 2 Receptor (D2R) and Sodium Iodide Symporter (NIS) Transgenes / 대한핵의학회잡지

PURPOSE: Both human NIS and mutant D2R transgenes are proposed as reporting system in transplanted cell tracking. Using hepatoma cell lines, we constructed a dual reporter system containing human sodium-iodide symporter (hNIS) and dopamine 2 receptor (D2R) and compared its characteristics. MATERIALS AND METHODS: The recombinant plasmid (pIRES-hNIS/D2R) was constructed with IRES (internal ribosome entry site) under control of the CMV promoter. pIRES-hNIS/D2R was transfected to human hepatoma SK-Hep1 cell line with lipofectamine. HEP-ND (SK-Hep1-hNIS/D2R) cells stably expressing hNIS and D2R was established by selection with G418 for two weeks. RT-PCR was performed to investigate the expression of both hNIS and D2R genes. The expressions of hNIS and D2R were measured by 125I uptake assays and receptor binding assays. Specific binding of D2R to [3H]spiperone was verified by Scatchard plot with (+) butaclamol as a specific inhibitor. K (d) and B (max) values were estimated. The correlation between hNIS and D2R expression was compared by using each clone. RESULTS: Similar quantities of hNIS and D2R genes were expressed on HEP-ND as RT-PCR assays. HEP-ND cells showed 30 to 40 fold higher radioiodine uptakes than those of parental SK-Hep1 cells. 125I uptake in HEP-ND cells was completely inhibited by KClO4, a NIS inhibitor. Specific binding to HEP-ND cells was saturable and the K (d) and B (max) values for HEP-ND cells were 2.92 nM, 745.25 fmol/mg protein and 2.91nM, 1323 fmole/mg protein in two clones, respectively. The radioiodine uptake by hNIS activity and D2R binding was highly correlated. CONCLUSION: We developed a dual positron and gamma imaging reporter system of hNIS and D2R in a stably transfected cell line. We expect that D2R and hNIS genes can complement mutually as a nuclear reporting system or that D2R can be used as reporter gene when hNIS gene were used as a treatment gene.