So Won Oh

Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: assessing the efficacy of 18F-FDG PET, 11C-methionine PET and perfusion MRI.

PURPOSE The authors analyzed the characteristics of perfusion magnetic resonance imaging (MRI), (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and (11)C-methionine (MET) PET to compare the efficacies of these modalities in making the distinction between radiation necrosis and tumor recurrence of high-grade glioma. PATIENTS AND METHODS Ten patients were evaluated with dynamic susceptibility contrast perfusion MRI, (11)C-MET PET and (18)F-FDG PET to visualize gadolinium-enhanced lesions during the post-radiation follow-up period. In the perfusion MRI, four regions of interest (ROIs) were identified and average values were calculated. A reference ROI of the same size was defined in the contralateral white matter to obtain the relative cerebral blood volume (rCBV). After coregistering the PET images with the MRI, we measured the maximum uptake values of the lesion and of the contralateral cerebral white matter as reference area to calculate the L(max)/R(max) ratio. RESULTS The rCBV was higher in the recurrence group than in the necrosis group (p=0.010). There was no difference between groups in terms of the L(max)/R(max) ratio as derived from the (18)F-FDG and (11)C-MET PET. CONCLUSION A quantitative rCBV as calculated from a perfusion MRI scan might be superior to the L(max)/R(max) ratio as derived from (18)F-FDG and (11)C-MET PET in order to distinguish a recurrence of high-grade glioma from radiation necrosis.

In vivo imaging of mGluR5 changes during epileptogenesis using [11C]ABP688 PET in pilocarpine-induced epilepsy rat model.

Introduction Metabotropic glutamate receptor 5 (mGluR5) that regulates glutamatergic neurotransmission contributes to pathophysiology of epilepsy. In this study, we monitored the changes of mGluR5 in vivo using [11C]ABP688 PET during the epileptogenesis in a pilocarpine-induced epilepsy rat model. Methods In vivo mGluR5 images were acquired using [11C]ABP688 microPET/CT in pilocarpine-induced chronic epilepsy rat models and controls. We also acquired microPET/CT at acute, subacute as well as chronic periods after status epilepticus. Non-displaceable binding potential (BPND) of [11C]ABP688 was calculated using simplified reference tissue model in a voxel-based manner. mGluR5 BPND of the rat brains of epilepsy models and controls were compared. Results Status epilepticus developed after pilocarpine administration and was followed by recurrent spontaneous seizures for more than 3 weeks. In chronic epilepsy rat model, BPND in hippocampus and amygdala was reduced on a voxel-based analysis. Temporal changes of mGluR5 BPND was also found. In acute period after status epilepticus, mGluR5 BPND was reduced in the whole brain. BPND of caudate-putamen was restored in subacute period, while BPND of the rest of the brain was still lower. In chronic period, global BPND was normalized except in hippocampus and amygdala. Conclusions In vivo imaging of mGluR5 using [11C]ABP688 microPET/CT could successfully reveal the regional changes of mGluR5 binding potential of the rat brain in a pilocarpine-induced epilepsy model. The temporal and spatial changes in mGluR5 availability suggest [11C]ABP688 PET imaging in epilepsy provide abnormal glutamatergic network during epileptogenesis.

Alternative Medical Treatment for Radioiodine-Refractory Thyroid Cancers

Thyroid cancer is one of the most rapidly increasing cancers in many countries. Although most thyroid cancers are differentiated cancers and easily treated with radioiodine (RI), a portion of differentiated and undifferentiated cancers is refractory not only to RI therapy, but also to radiotherapy and chemotherapy. Thus, various alternative therapies have been tested in RI-refractory thyroid cancers. These alternative therapies include two major categories: redifferentiation therapy and recent molecular target therapy. Several clinical trials have investigated these therapies. They demonstrated potential effects of the therapies, although the results have been somewhat limited so far. Thus, the future strategy for undifferentiated thyroid cancers will involve individualized, lesion-specific, and combined therapy. In this review, the basic mechanism of each redifferentiation and molecular target therapy is discussed, and results of recent clinical trials using these therapeutic agents are summarized.

In vivo Monitoring of microRNA Biogenesis Using Reporter Gene Imaging

MicroRNAs are small noncoding RNAs regulating gene expression, through base paring with their target mRNAs, which have been actively investigated as key regulators in a wide range of biological processes. Conventional methods such as Northern blot are generally time-consuming, non-repeatable, and cannot be applied in vivo due to the requirement for cell fixation. Therefore, a noninvasive imaging system is required for the monitoring of microRNA biogenesis to understand the versatile functions of microRNAs in vivo as well as in vitro and to accelerate the clinical application of microRNA-based therapy. In this paper, we reviewed noninvasive molecular imaging systems for the monitoring of the biogenesis of microRNAs and post-transcriptional regulation of genes by microRNAs and the roles of microRNAs in various biological processes.

Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer

Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (<1.0 ng/mL). Various factors including age, off-Tg, and histopathology were analyzed to predict ablation success rates. Of 176 patients, 68.8% (n = 121) who achieved successful remnant ablation were classified into Group A, and the remaining 55 were classified into Group B. Group A presented with significantly lower off-Tg at the first radioiodine administration (pre-ablative Tg) than those of Group B (1.2 ± 2.3 ng/mL vs. 6.2 ± 15.2 ng/mL, P = 0.027). Pre-ablative Tg was the only significant factor related with ablation success rates. Diagnostic performances of pre-ablative Tg < 10.0 ng/mL were sensitivity of 99.1%, specificity of 14.0%, positive predictive value of 71.1%, and negative predictive value of 87.5%, respectively. Single administration of low radioiodine activity could be sufficient for remnant thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation. Graphical Abstract

Diagnostic Performance of Three-Phase Bone Scan for Complex Regional Pain Syndrome Type 1 with Optimally Modified Image Criteria

PurposeAlthough the three-phase bone scan (TBPS) is one of the widely used imaging studies for diagnosing complex regional pain syndrome type I (CRPS-1), there is some controversy regarding the TPBS image criteria for CRPS-1. In this study, we modified the image criteria using image pattern and quantitative analysis in the patients diagnosed using the most recent consensus clinical diagnostic criteria.Materials and MethodsThe study included 140 patients with suspected CRPS-1 (CRPS-1, n = 79; non-CRPS, n = 61; mean age 39 ± 15 years) who underwent TPBS. The clinical diagnostic criteria for CRPS-1 revised by the Budapest consensus group were used for confirmative diagnosis. Patients were classified according to flow/pool and delayed uptake (DU) image patterns, and the time interval between the initiating event and TPBS (TIevent-scan). Quantitative analysis for lesion-to-contralateral ratio (LCR) was performed. Modified TPBS image criteria were created and evaluated for optimal diagnostic performance.ResultsBoth increased and decreased periarticular DU were significant image findings for CRPS-1 (CRPS-1 positive-rate = 73% in the increased DU group, 75% in the decreased DU group). The TIevent-scan did not differ significantly between the different image pattern groups. Quantitative analysis revealed an LCR of 1.43 was the optimal cutoff value for CRPS-1 and diagnostic performance was significantly improved in the increased DU group (area under the curve = 0.732). Given the modified image criteria, the sensitivity and specificity of TPBS for diagnosing CRPS-1 were 80% and 72%, respectively.ConclusionsOptimally modified TPBS image criteria for CRPS-1 were suggested using image pattern and quantitative analysis. With the criteria, TPBS is an effective imaging study for CRPS-1 even with the most recent consensus clinical diagnostic criteria.

Pulmonary Artery Embolotherapy in a Patient with Type I Hepatopulmonary Syndrome after Liver Transplantation

Although liver transplantation (LT) is the only effective treatment option for hepatopulmonary syndrome (HPS), the post-LT morbidity and mortality have been high for patients with severe HPS. We performed post-LT embolotherapy in a 10-year-old boy who had severe type I HPS preoperatively, but he failed to recover early from his hypoxemic symptoms after an LT. Multiple embolizations were then successfully performed on the major branches that formed the abnormal vascular structures. After the embolotherapy, the patient had symptomatic improvement and he was discharged without complications.

Breast Sparganosis Incidentally Detected by FDG PET/CT

Sparganosis is a rare, parasitic infection that is caused by the plercercoid tapeworm larvae of the genus Spirometra. Sparganosis is transmitted by ingestion of larvae-containing water or intermediate hosts, such as raw amphibians, and usually presented with a subcutaneous nodule in the abdominal wall, extremities, and genital organs. Among the various involved organs, the breast is a seldom encountered site for sparganosis. However, breast sparganosis has clinical importance, since it is generally presented with an indolent palpable mass that mimics malignancy, even without evidence of inflammation. Herein, we report a case of breast sparganosis that was detected incidentally by FDG PET/CT during staging work ups in a patient with gall bladder cancer.

Influence of Androgen Deprivation Therapy on the Uptake of PSMA-Targeted Agents: Emerging Opportunities and Challenges

Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer.

In vivo bioluminescence imaging of transplanted mesenchymal stem cells as a potential source for pancreatic regeneration.

Stem cell therapy has been studied intensively as a promising therapeutic strategy toward a cure for diabetes. To study the effect of mesenchymal stem cell (MSC) transplantation for pancreatic regeneration, we monitored the localization and distribution of transplanted MSCs by bioluminescence imaging in a mouse model. Bone marrow MSCs were isolated and transfected with a highly sensitive firefly luciferase reporter gene. To assess the efficiency of MSC transplantation, a partially pancreatectomized (PPx) mouse model was used. Transplanted MSCs were monitored by confocal microscopy and in vivo bioluminescence imaging. Daily blood glucose levels and glucose tolerance were measured. Insulin-secreting beta cells were immunostained, and insulin levels were measured via enzyme-linked immunosorbent assay. Bioluminescence signals were clearly detected from the transplanted MSCs in the pancreatic region regardless of injection route. However, locally injected MSCs exhibited more rapid proliferation than ductally injected MSCs. PPx mice harboring transplanted MSCs gradually recovered from impaired glucose tolerance. Although insulin secretion was not observed in MSCs, transplanted MSCs facilitate the injured pancreas to recover its function. In vivo optical imaging of transplanted MSCs using a highly sensitive luciferase reporter enables the assessment of MSC transplantation efficiency in a PPx mouse model.Stem cell therapy has been studied intensively as a promising therapeutic strategy toward a cure for diabetes. To study the effect of mesenchymal stem cell (MSC) transplantation for pancreatic regeneration, we monitored the localization and distribution of transplanted MSCs by bioluminescence imaging in a mouse model. Bone marrow MSCs were isolated and transfected with a highly sensitive firefly luciferase reporter gene. To assess the efficiency of MSC transplantation, a partially pancreatectomized (PPx) mouse model was used. Transplanted MSCs were monitored by confocal microscopy and in vivo bioluminescence imaging. Daily blood glucose levels and glucose tolerance were measured. Insulin-secreting beta cells were immunostained, and insulin levels were measured via enzyme-linked immunosorbent assay. Bioluminescence signals were clearly detected from the transplanted MSCs in the pancreatic region regardless of injection route. However, locally injected MSCs exhibited more rapid proliferation than ductally injected MSCs. PPx mice harboring transplanted MSCs gradually recovered from impaired glucose tolerance. Although insulin secretion was not observed in MSCs, transplanted MSCs facilitate the injured pancreas to recover its function. In vivo optical imaging of transplanted MSCs using a highly sensitive luciferase reporter enables the assessment of MSC transplantation efficiency in a PPx mouse model.